21. | Tahtinen, S; Feola, S; Capasso, C; Laustio, N; Groeneveldt, C; Ylosmaki, EO; Ylosmaki, L; Martins, B; Fusciello, M; Medeot, M; Tagliamonte, M; Chiaro, J; Hamdan, F; Peltonen, K; Ranki, T; Buonaguro, L; Cerullo, V Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy Journal Article In: Cancer Research, 80 (12), pp. 2575–2585, 2020, ISSN: 0008-5472. Links | iCAN PI: Cerullo, Vincenzo @article{c12030e61b3247b1a986a68caf27703f, title = {Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy}, author = {Tahtinen, S; Feola, S; Capasso, C; Laustio, N; Groeneveldt, C; Ylosmaki, EO; Ylosmaki, L; Martins, B; Fusciello, M; Medeot, M; Tagliamonte, M; Chiaro, J; Hamdan, F; Peltonen, K; Ranki, T; Buonaguro, L; Cerullo, V}, editor = {Cerullo, Vincenzo}, doi = {10.1158/0008-5472.CAN-19-2062}, issn = {0008-5472}, year = {2020}, date = {2020-01-01}, journal = {Cancer Research}, volume = {80}, number = {12}, pages = {2575--2585}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
22. | Zhang, K; Pekcan Erkan, E; Dai, J; Andersson, N; Kaipio, K; , T; Mansuri, N; Huhtinen, K; Carpen, O; Hynninen, J; , S; Oikkonen, J; Hakkinen, A; Hautaniemi, S; Vaharautio, A In: 2020. Links | iCAN PI: Vähärautio, Anne @article{Zhang2020, title = {Analysis of single-cell RNA-seq data from ovarian cancer samples before and after chemotherapy links stress-related transcriptional profile with chemotherapy resistance}, author = {Zhang, K; Pekcan Erkan, E; Dai, J; Andersson, N; Kaipio, K; , T; Mansuri, N; Huhtinen, K; Carpen, O; Hynninen, J; , S; Oikkonen, J; Hakkinen, A; Hautaniemi, S; Vaharautio, A}, editor = {Vähärautio, Anne}, url = {https://doi.org/10.1101/2020.06.06.138362}, doi = {10.1101/2020.06.06.138362}, year = {2020}, date = {2020-01-01}, publisher = {Cold Spring Harbor Laboratory}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
23. | Dziubanska-Kusibab, PJ; Berger, H; Battistini, F; Bouwman, BAM; Iftekhar, A; Katainen, R; Cajuso, T; Crosetto, N; Orozco, M; Aaltonen, LA; Meyer, TF Colibactin DNA-damage signature indicates mutational impact in colorectal cancer Journal Article In: Nature Medicine, 26 (7), pp. 1063–+, 2020, ISSN: 1078-8956. Links | iCAN PI: Aaltonen, Lauri A. @article{b733ab3a06014e768f40d258c5749837, title = {Colibactin DNA-damage signature indicates mutational impact in colorectal cancer}, author = {Dziubanska-Kusibab, PJ; Berger, H; Battistini, F; Bouwman, BAM; Iftekhar, A; Katainen, R; Cajuso, T; Crosetto, N; Orozco, M; Aaltonen, LA; Meyer, TF}, editor = {Aaltonen, Lauri A.}, doi = {10.1038/s41591-020-0908-2}, issn = {1078-8956}, year = {2020}, date = {2020-01-01}, journal = {Nature Medicine}, volume = {26}, number = {7}, pages = {1063--+}, publisher = {Nature Publishing Group}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
24. | Joensuu, H; Eriksson, M; Hall, KS; Reichardt, A; Hermes, B; Schutte, J; Cameron, S; Hohenberger, P; Jost, PJ; Al-Batran, SE; Lindner, LH; Bauer, S; Wardelmann, E; Nilsson, B; Kallio, R; Jaakkola, P; Junnila, J; Alvegard, T; Reichardt, P In: JAMA Oncology, 6 (8), pp. 1241–1246, 2020, ISSN: 2374-2437. Links | iCAN PI: Joensuu, Heikki @article{b572e731a0c24010a5434856aec284c1, title = {Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors An Analysis of a Randomized Clinical Trial After 10-Year Follow-up}, author = {Joensuu, H; Eriksson, M; Hall, KS; Reichardt, A; Hermes, B; Schutte, J; Cameron, S; Hohenberger, P; Jost, PJ; Al-Batran, SE; Lindner, LH; Bauer, S; Wardelmann, E; Nilsson, B; Kallio, R; Jaakkola, P; Junnila, J; Alvegard, T; Reichardt, P}, editor = {Joensuu, Heikki}, doi = {10.1001/jamaoncol.2020.2091}, issn = {2374-2437}, year = {2020}, date = {2020-01-01}, journal = {JAMA Oncology}, volume = {6}, number = {8}, pages = {1241--1246}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
25. | Dufva, O; Polonen, P; Bruck, O; Keranen, MA; Klievink, J; Mehtonen, J; Huuhtanen, J; Kumar, A; Malani, D; Siitonen, S; Kankainen, M; Ghimire, B; Lahtela, J; Mattila, P; Vaha-Koskela, M; Wennerberg, K; Granberg, K; Leivonen, SK; Meriranta, L; Heckman, C; Leppa, S; Nykter, M; Lohi, O; Heinaniemi, M; Mustjoki, S Immunogenomic Landscape of Hematological Malignancies Journal Article In: Cancer Cell, 38 (3), pp. 380–399, 2020, ISSN: 1535-6108. Links | iCAN PI: Mustjoki, Satu @article{8c601b31f8be41bca55a460e5c26c079, title = {Immunogenomic Landscape of Hematological Malignancies}, author = {Dufva, O; Polonen, P; Bruck, O; Keranen, MA; Klievink, J; Mehtonen, J; Huuhtanen, J; Kumar, A; Malani, D; Siitonen, S; Kankainen, M; Ghimire, B; Lahtela, J; Mattila, P; Vaha-Koskela, M; Wennerberg, K; Granberg, K; Leivonen, SK; Meriranta, L; Heckman, C; Leppa, S; Nykter, M; Lohi, O; Heinaniemi, M; Mustjoki, S}, editor = {Mustjoki, Satu}, doi = {10.1016/j.ccell.2020.06.002}, issn = {1535-6108}, year = {2020}, date = {2020-01-01}, journal = {Cancer Cell}, volume = {38}, number = {3}, pages = {380--399}, publisher = {Cell Press}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
26. | Seppala, TT; Zimmerman, JW; Sereni, E; Plenker, D; Suri, R; Rozich, N; Blair, A; Thomas, DL; Teinor, J; Javed, A; Patel, H; Cameron, JL; Burns, WR; He, J; Tuveson, DA; Jaffee, EM; Eshleman, J; Szabolcs, A; Ryan, DP; Ting, DVT; Wolfgang, CL; Burkhart, RA Patient-derived Organoid Pharmacotyping is a Clinically Tractable Strategy for Precision Medicine in Pancreatic Cancer Journal Article In: 272 (3), pp. 427–435, 2020, ISSN: 0003-4932. Links | iCAN PI: Seppälä, Toni @article{9ca4a43f95ba41df8a76ba2a7f6042a3, title = {Patient-derived Organoid Pharmacotyping is a Clinically Tractable Strategy for Precision Medicine in Pancreatic Cancer}, author = {Seppala, TT; Zimmerman, JW; Sereni, E; Plenker, D; Suri, R; Rozich, N; Blair, A; Thomas, DL; Teinor, J; Javed, A; Patel, H; Cameron, JL; Burns, WR; He, J; Tuveson, DA; Jaffee, EM; Eshleman, J; Szabolcs, A; Ryan, DP; Ting, DVT; Wolfgang, CL; Burkhart, RA}, editor = {Seppälä, Toni}, doi = {10.1097/SLA.0000000000004200}, issn = {0003-4932}, year = {2020}, date = {2020-01-01}, volume = {272}, number = {3}, pages = {427--435}, publisher = {Lippincott williams & wilkins}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
27. | Mars, N; Koskela, JT; Ripatti, P; Kiiskinen, TTJ; Havulinna, AS; Lindbohm, JV; Ahola-Olli, A; Kurki, M; Karjalainen, J; Palta, P; Neale, BM; Daly, M; Salomaa, V; Palotie, A; Widen, E; Ripatti, S Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers Journal Article In: Nature Medicine, 26 (4), pp. 549–557, 2020, ISSN: 1078-8956. Abstract | Links | iCAN PI: Ripatti, Samuli @article{312889ddf0964c72a7ca3db2995b99f1, title = {Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers}, author = {Mars, N; Koskela, JT; Ripatti, P; Kiiskinen, TTJ; Havulinna, AS; Lindbohm, JV; Ahola-Olli, A; Kurki, M; Karjalainen, J; Palta, P; Neale, BM; Daly, M; Salomaa, V; Palotie, A; Widen, E; Ripatti, S}, editor = {Ripatti, Samuli}, doi = {10.1038/s41591-020-0800-0}, issn = {1078-8956}, year = {2020}, date = {2020-01-01}, journal = {Nature Medicine}, volume = {26}, number = {4}, pages = {549--557}, publisher = {Nature Publishing Group}, abstract = {Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases1,2,3. We estimated their added value in clinical risk prediction of five common diseases, using large-scale biobank data (FinnGen; n = 135,300) and the FINRISK study with clinical risk factors to test genome-wide PRSs for coronary heart disease, type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer. We evaluated the lifetime risk at different PRS levels, and the impact on disease onset and on prediction together with clinical risk scores. Compared to having an average PRS, having a high PRS contributed 21% to 38% higher lifetime risk, and 4 to 9 years earlier disease onset. PRSs improved model discrimination over age and sex in type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer, and over clinical risk in type 2 diabetes, breast cancer and prostate cancer. In all diseases, PRSs improved reclassification over clinical thresholds, with the largest net reclassification improvements for early-onset coronary heart disease, atrial fibrillation and prostate cancer. This study provides evidence for the additional value of PRSs in clinical disease prediction. The practical applications of polygenic risk information for stratified screening or for guiding lifestyle and medical interventions in the clinical setting remain to be defined in further studies.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases1,2,3. We estimated their added value in clinical risk prediction of five common diseases, using large-scale biobank data (FinnGen; n = 135,300) and the FINRISK study with clinical risk factors to test genome-wide PRSs for coronary heart disease, type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer. We evaluated the lifetime risk at different PRS levels, and the impact on disease onset and on prediction together with clinical risk scores. Compared to having an average PRS, having a high PRS contributed 21% to 38% higher lifetime risk, and 4 to 9 years earlier disease onset. PRSs improved model discrimination over age and sex in type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer, and over clinical risk in type 2 diabetes, breast cancer and prostate cancer. In all diseases, PRSs improved reclassification over clinical thresholds, with the largest net reclassification improvements for early-onset coronary heart disease, atrial fibrillation and prostate cancer. This study provides evidence for the additional value of PRSs in clinical disease prediction. The practical applications of polygenic risk information for stratified screening or for guiding lifestyle and medical interventions in the clinical setting remain to be defined in further studies. |
28. | Wei, AH; Dohner, H; Pocock, C; Montesinos, P; Afanasyev, B; Dombret, H; Ravandi, F; Sayar, H; Jang, JH; Porkka, K; Selleslag, D; Sandhu, I; Turgut, M; Giai, V; Ofran, Y; Cakar, MK; de Sousa, AB; Rybka, J; Frairia, C; Borin, L; Beltrami, G; Cermak, J; Ossenkoppele, GJ; La Torre, I; Skikne, B; Kumar, K; Dong, Q; Beach, CL; Roboz, GJ Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission Journal Article In: New England Journal of Medicine, 383 (26), pp. 2526–2537, 2020, ISSN: 0028-4793. Links | iCAN PI: Porkka, Kimmo @article{550bba880abe44058b7755221f2c180f, title = {Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission}, author = {Wei, AH; Dohner, H; Pocock, C; Montesinos, P; Afanasyev, B; Dombret, H; Ravandi, F; Sayar, H; Jang, JH; Porkka, K; Selleslag, D; Sandhu, I; Turgut, M; Giai, V; Ofran, Y; Cakar, MK; de Sousa, AB; Rybka, J; Frairia, C; Borin, L; Beltrami, G; Cermak, J; Ossenkoppele, GJ; La Torre, I; Skikne, B; Kumar, K; Dong, Q; Beach, CL; Roboz, GJ}, editor = {Porkka, Kimmo}, doi = {10.1056/NEJMoa2004444}, issn = {0028-4793}, year = {2020}, date = {2020-01-01}, journal = {New England Journal of Medicine}, volume = {383}, number = {26}, pages = {2526--2537}, publisher = {Massachusetts Medical Society}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
29. | Bychkov, D; Linder, N; Tiulpin, A; Kucukel, H; Lundin, M; Nordling, S; Sihto, H; Isola, J; Lehtimaki, T; Kellokumpu-Lehtinen, PL; von Smitten, K; Joensuu, H; Lundin, J Deep learning identifies morphological features in breast cancer predictive of cancer ERBB2 status and trastuzumab treatment efficacy Journal Article In: Scientific Reports, 11 (1), 2021, ISSN: 2045-2322. Links | iCAN PI: Lundin, Johan @article{2c78eab400dd4a03a476f791caa2ff62, title = {Deep learning identifies morphological features in breast cancer predictive of cancer ERBB2 status and trastuzumab treatment efficacy}, author = {Bychkov, D; Linder, N; Tiulpin, A; Kucukel, H; Lundin, M; Nordling, S; Sihto, H; Isola, J; Lehtimaki, T; Kellokumpu-Lehtinen, PL; von Smitten, K; Joensuu, H; Lundin, J}, editor = {Lundin, Johan}, doi = {10.1038/s41598-021-83102-6}, issn = {2045-2322}, year = {2021}, date = {2021-01-01}, journal = {Scientific Reports}, volume = {11}, number = {1}, publisher = {Nature Publishing Group}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
30. | Robert, C; Long, GV; Brady, B; Dutriaux, C; Di Giacomo, AM; Mortier, L; Rutkowski, P; Hassel, JC; McNeil, CM; Kalinka, EA; Lebbe, C; Charles, J; Hernberg, MM; Savage, KJ; Chiarion-Sileni, V; Mihalcioiu, C; Mauch, C; Arance, A; Cognetti, F; Ny, L; Schmidt, H; Schadendorf, D; Gogas, H; Zoco, J; Re, S; Ascierto, PA; Atkinson, V Five-Year Outcomes With Nivolumab in Patients With Wild-Type BRAF Advanced Melanoma Journal Article In: Journal of Clinical Oncology, 38 (33), 2020, ISSN: 0732-183X. Links | iCAN PI: Hernberg, Mikaela @article{6b6aa76e9b944691b7efe36b40f5b771, title = {Five-Year Outcomes With Nivolumab in Patients With Wild-Type BRAF Advanced Melanoma}, author = {Robert, C; Long, GV; Brady, B; Dutriaux, C; Di Giacomo, AM; Mortier, L; Rutkowski, P; Hassel, JC; McNeil, CM; Kalinka, EA; Lebbe, C; Charles, J; Hernberg, MM; Savage, KJ; Chiarion-Sileni, V; Mihalcioiu, C; Mauch, C; Arance, A; Cognetti, F; Ny, L; Schmidt, H; Schadendorf, D; Gogas, H; Zoco, J; Re, S; Ascierto, PA; Atkinson, V}, editor = {Hernberg, Mikaela}, doi = {10.1200/JCO.20.00995}, issn = {0732-183X}, year = {2020}, date = {2020-01-01}, journal = {Journal of Clinical Oncology}, volume = {38}, number = {33}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
31. | Loi, S; Drubay, D; Adams, S; Pruneri, G; Francis, PA; Lacroix-Triki, M; Joensuu, H; Dieci, MV; Badve, S; Demaria, S; Gray, R; Munzone, E; Lemonnier, J; Sotiriou, C; Piccart, MJ; Kellokumpu-Lehtinen, PL; Vingiani, A; Gray, K; Andre, F; Denkert, C; Salgado, R; Michiels, S Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers Journal Article In: Journal of Clinical Oncology, 37 (7), pp. 559–+, 2019, ISSN: 0732-183X. Links | iCAN PI: Joensuu, Heikki @article{d76870db5f7e4994984d5241a5ce4efa, title = {Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers}, author = {Loi, S; Drubay, D; Adams, S; Pruneri, G; Francis, PA; Lacroix-Triki, M; Joensuu, H; Dieci, MV; Badve, S; Demaria, S; Gray, R; Munzone, E; Lemonnier, J; Sotiriou, C; Piccart, MJ; Kellokumpu-Lehtinen, PL; Vingiani, A; Gray, K; Andre, F; Denkert, C; Salgado, R; Michiels, S}, editor = {Joensuu, Heikki}, doi = {10.1200/JCO.18.01010}, issn = {0732-183X}, year = {2019}, date = {2019-01-01}, journal = {Journal of Clinical Oncology}, volume = {37}, number = {7}, pages = {559--+}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
32. | Wirta, EV; Szeto, S; Hanninen, U; Ahtiainen, M; Bohm, J; Mecklin, JP; Aaltonen, LA; Seppala, TT Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions Journal Article In: Cancers, 12 (8), 2020, ISSN: 2072-6694. Abstract | Links | iCAN PI: Seppälä, Toni @article{bdbe6bf6a71a411d8fabce8fffd7bad2, title = {Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions}, author = {Wirta, EV; Szeto, S; Hanninen, U; Ahtiainen, M; Bohm, J; Mecklin, JP; Aaltonen, LA; Seppala, TT}, editor = {Seppälä, Toni}, doi = {10.3390/cancers12082018}, issn = {2072-6694}, year = {2020}, date = {2020-01-01}, journal = {Cancers}, volume = {12}, number = {8}, publisher = {MDPI}, abstract = {Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance. |
33. | Bruck, O; Dufva, O; Hohtari, H; Blom, S; Turkki, R; Ilander, M; Kovanen, P; Pallaud, C; Ramos, PM; Lahteenmaki, H; Valimaki, K; El Missiry, M; Ribeiro, A; Kallioniemi, O; Porkka, K; Pellinen, T; Mustjoki, S Immune profiles in acute myeloid leukemia bone marrow associate with patient age, T-cell receptor clonality, and survival Journal Article In: Blood advances, 4 (2), pp. 274–286, 2020, ISSN: 2473-9529. Links | iCAN PI: Mustjoki, Satu @article{325eb63ea2f048548a46ee5986d64569, title = {Immune profiles in acute myeloid leukemia bone marrow associate with patient age, T-cell receptor clonality, and survival}, author = {Bruck, O; Dufva, O; Hohtari, H; Blom, S; Turkki, R; Ilander, M; Kovanen, P; Pallaud, C; Ramos, PM; Lahteenmaki, H; Valimaki, K; El Missiry, M; Ribeiro, A; Kallioniemi, O; Porkka, K; Pellinen, T; Mustjoki, S}, editor = {Mustjoki, Satu}, doi = {10.1182/bloodadvances.2019000792}, issn = {2473-9529}, year = {2020}, date = {2020-01-01}, journal = {Blood advances}, volume = {4}, number = {2}, pages = {274--286}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
34. | Murumagi, A; Ungureanu, D; Arjama, M; Butzow, R; Lohi, J; Sariola, H; Kanerva, J; Koskenvuo, M; Kallioniemi, O STRN-ALK rearranged pediatric malignant peritoneal mesothelioma - Functional testing of 527 cancer drugs in patient-derived cancer cells Journal Article In: Translational oncology, 14 (4), 2021, ISSN: 1936-5233. Links | iCAN PI: Kallioniemi, Olli @article{6c8d68fde2764dd799b15537db2c3c13, title = {STRN-ALK rearranged pediatric malignant peritoneal mesothelioma - Functional testing of 527 cancer drugs in patient-derived cancer cells}, author = {Murumagi, A; Ungureanu, D; Arjama, M; Butzow, R; Lohi, J; Sariola, H; Kanerva, J; Koskenvuo, M; Kallioniemi, O}, editor = {Kallioniemi, Olli}, doi = {10.1016/j.tranon.2021.101027}, issn = {1936-5233}, year = {2021}, date = {2021-01-01}, journal = {Translational oncology}, volume = {14}, number = {4}, publisher = {EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
35. | Majumder, MM; Leppa, AM; Hellesoy, M; Dowling, P; Malyutina, A; Kopperud, R; Bazou, D; Andersson, E; Parsons, A; Tang, J; Kallioniemi, O; Mustjoki, S; O'Gorman, P; Wennerberg, K; Porkka, K; Gjertsen, BT; Heckman, CA In: Haematologica, 105 (6), pp. 1527–1538, 2020, ISSN: 0390-6078. Links | iCAN PI: Heckman, Caroline A. @article{e4fb5d887a2c4b69932b9b446a1b10e6, title = {Multi-parametric single cell evaluation defines distinct drug responses in healthy hematologic cells that are retained in corresponding malignant cell types}, author = {Majumder, MM; Leppa, AM; Hellesoy, M; Dowling, P; Malyutina, A; Kopperud, R; Bazou, D; Andersson, E; Parsons, A; Tang, J; Kallioniemi, O; Mustjoki, S; O'Gorman, P; Wennerberg, K; Porkka, K; Gjertsen, BT; Heckman, CA}, editor = {Heckman, Caroline A.}, doi = {10.3324/haematol.2019.217414}, issn = {0390-6078}, year = {2020}, date = {2020-01-01}, journal = {Haematologica}, volume = {105}, number = {6}, pages = {1527--1538}, publisher = {FERRATA STORTI FOUNDATION}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
36. | Rajamäki K*, Taira A*, Katainen R, Välimäki N, Kuosmanen A, Plaketti RM, Seppälä TT, Ahtiainen M, Wirta EV, Vartiainen E, Sulo P, Ravantti J, Lehtipuro S, Granberg KJ, Nykter M, Tanskanen T, Ristimäki A, Koskensalo S, Renkonen-Sinisalo L, Lepistö A, Böhm J, Taipale J, Mecklin JP, Aavikko M, Palin K, Aaltonen LA. Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease–Associated Colorectal Cancer Journal Article In: Gastroenterology, 161 (2), pp. 592–607, 2021, ISSN: 0016-5085. Abstract | Links | iCAN PI: Aaltonen, Lauri A. @article{c3a9ff778aac438e9bd8952fdfa2e326, title = {Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease–Associated Colorectal Cancer}, author = {Rajamäki K*, Taira A*, Katainen R, Välimäki N, Kuosmanen A, Plaketti RM, Seppälä TT, Ahtiainen M, Wirta EV, Vartiainen E, Sulo P, Ravantti J, Lehtipuro S, Granberg KJ, Nykter M, Tanskanen T, Ristimäki A, Koskensalo S, Renkonen-Sinisalo L, Lepistö A, Böhm J, Taipale J, Mecklin JP, Aavikko M, Palin K, Aaltonen LA.}, editor = {Aaltonen, Lauri A.}, doi = {10.1053/j.gastro.2021.04.042}, issn = {0016-5085}, year = {2021}, date = {2021-01-01}, journal = {Gastroenterology}, volume = {161}, number = {2}, pages = {592–607}, publisher = {W B SAUNDERS CO-ELSEVIER INC}, abstract = {Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Results Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Conclusions Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Results Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Conclusions Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD. |
37. | Bao, EL; Nandakumar, SK; Liao, XT; Bick, AG; Karjalainen, J; Tabaka, M; Gan, OI; Havulinna, AS; Kiiskinen, TTJ; Lareau, CA; Portilla, ALD; Li, B; Emdin, C; Codd, V; Nelson, CP; Walker, CJ; Churchhouse, C; de la Chapelle, A; Klein, DE; Nilsson, B; Wilson, PWF; Cho, K; Pyarajan, S; Gaziano, JM; Samani, NJ; Regev, A; Palotie, A; Neale, BM; Dick, JE; Natarajan, P; O'Donnell, CJ; Daly, MJ; Milyavsky, M; Kathiresan, S; Sankaran, VG Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells Journal Article In: Nature, 586 (7831), pp. 769–775, 2020, ISSN: 0028-0836. Abstract | Links | iCAN PI: Daly, Mark J. @article{016d93cb96d84cb1addc2f07a0f18e7f, title = {Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells}, author = {Bao, EL; Nandakumar, SK; Liao, XT; Bick, AG; Karjalainen, J; Tabaka, M; Gan, OI; Havulinna, AS; Kiiskinen, TTJ; Lareau, CA; Portilla, ALD; Li, B; Emdin, C; Codd, V; Nelson, CP; Walker, CJ; Churchhouse, C; de la Chapelle, A; Klein, DE; Nilsson, B; Wilson, PWF; Cho, K; Pyarajan, S; Gaziano, JM; Samani, NJ; Regev, A; Palotie, A; Neale, BM; Dick, JE; Natarajan, P; O'Donnell, CJ; Daly, MJ; Milyavsky, M; Kathiresan, S; Sankaran, VG}, editor = {Daly, Mark J.}, doi = {10.1038/s41586-020-2786-7}, issn = {0028-0836}, year = {2020}, date = {2020-01-01}, journal = {Nature}, volume = {586}, number = {7831}, pages = {769–775}, publisher = {Nature Publishing Group}, abstract = {Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs that is among the highest known for cancers1. However, only a limited number of genetic risk loci have been identified, and the underlying biological mechanisms that lead to the acquisition of MPNs remain unclear. Here, by conducting a large-scale genome-wide association study (3,797 cases and 1,152,977 controls), we identify 17 MPN risk loci (P < 5.0 × 10−8), 7 of which have not been previously reported. We find that there is a shared genetic architecture between MPN risk and several haematopoietic traits from distinct lineages; that there is an enrichment for MPN risk variants within accessible chromatin of HSCs; and that increased MPN risk is associated with longer telomere length in leukocytes and other clonal haematopoietic states—collectively suggesting that MPN risk is associated with the function and self-renewal of HSCs. We use gene mapping to identify modulators of HSC biology linked to MPN risk, and show through targeted variant-to-function assays that CHEK2 and GFI1B have roles in altering the function of HSCs to confer disease risk. Overall, our results reveal a previously unappreciated mechanism for inherited MPN risk through the modulation of HSC function.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs that is among the highest known for cancers1. However, only a limited number of genetic risk loci have been identified, and the underlying biological mechanisms that lead to the acquisition of MPNs remain unclear. Here, by conducting a large-scale genome-wide association study (3,797 cases and 1,152,977 controls), we identify 17 MPN risk loci (P < 5.0 × 10−8), 7 of which have not been previously reported. We find that there is a shared genetic architecture between MPN risk and several haematopoietic traits from distinct lineages; that there is an enrichment for MPN risk variants within accessible chromatin of HSCs; and that increased MPN risk is associated with longer telomere length in leukocytes and other clonal haematopoietic states—collectively suggesting that MPN risk is associated with the function and self-renewal of HSCs. We use gene mapping to identify modulators of HSC biology linked to MPN risk, and show through targeted variant-to-function assays that CHEK2 and GFI1B have roles in altering the function of HSCs to confer disease risk. Overall, our results reveal a previously unappreciated mechanism for inherited MPN risk through the modulation of HSC function. |
38. | Rodriguez, A; Zhang, KY; Farkkila, A; Filiatrault, J; Yang, CY; Velazquez, M; Furutani, E; Goldman, DC; de Teresa, BG; Garza-Mayen, G; McQueen, K; Sambel, LA; Molina, B; Torres, L; Gonzalez, M; Vadillo, E; Pelayo, R; Fleming, WH; Grompe, M; Shimamura, A; Hautaniemi, S; Greenberger, J; Frias, S; Parmar, K; D'Andrea, AD MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia Journal Article In: Cell Stem Cell, 28 (1), pp. 33–+, 2021, ISSN: 1934-5909. Links | iCAN PI: Hautaniemi, Sampsa; Färkkilä, Anniina @article{b697485a2dfb419aa3e6467987b91412, title = {MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia}, author = {Rodriguez, A; Zhang, KY; Farkkila, A; Filiatrault, J; Yang, CY; Velazquez, M; Furutani, E; Goldman, DC; de Teresa, BG; Garza-Mayen, G; McQueen, K; Sambel, LA; Molina, B; Torres, L; Gonzalez, M; Vadillo, E; Pelayo, R; Fleming, WH; Grompe, M; Shimamura, A; Hautaniemi, S; Greenberger, J; Frias, S; Parmar, K; D'Andrea, AD}, editor = {Hautaniemi, Sampsa; Färkkilä, Anniina}, doi = {10.1016/j.stem.2020.09.004}, issn = {1934-5909}, year = {2021}, date = {2021-01-01}, journal = {Cell Stem Cell}, volume = {28}, number = {1}, pages = {33--+}, publisher = {Cell Press}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
39. | Holmstrom, O; Linder, N; Kaingu, H; Mbuuko, N; Mbete, J; Kinyua, F; Tornquist, S; Muinde, M; Krogerus, L; Lundin, M; Diwan, V; Lundin, J Point-of-Care Digital Cytology With Artificial Intelligence for Cervical Cancer Screening in a Resource-Limited Setting Journal Article In: JAMA Network Open, 4 (3), pp. e211740–e211740, 2021, ISSN: 2574-3805. Links | iCAN PI: Lundin, Johan @article{1d71467deddd4d3fbb81e1addb4f8bf8, title = {Point-of-Care Digital Cytology With Artificial Intelligence for Cervical Cancer Screening in a Resource-Limited Setting}, author = {Holmstrom, O; Linder, N; Kaingu, H; Mbuuko, N; Mbete, J; Kinyua, F; Tornquist, S; Muinde, M; Krogerus, L; Lundin, M; Diwan, V; Lundin, J}, editor = {Lundin, Johan}, doi = {10.1001/jamanetworkopen.2021.1740}, issn = {2574-3805}, year = {2021}, date = {2021-01-01}, journal = {JAMA Network Open}, volume = {4}, number = {3}, pages = {e211740--e211740}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
40. | Tanoli, Z; Vaha-Koskela, M; Aittokallio, T Artificial intelligence, machine learning, and drug repurposing in cancer Journal Article In: Expert opinion on drug discovery, 16 (9), pp. 977–989, 2021, ISSN: 1746-0441. Links | iCAN PI: Aittokallio, Tero @article{900e385c47c44079afab0f51a1e475cb, title = {Artificial intelligence, machine learning, and drug repurposing in cancer}, author = {Tanoli, Z; Vaha-Koskela, M; Aittokallio, T}, editor = {Aittokallio, Tero}, doi = {10.1080/17460441.2021.1883585}, issn = {1746-0441}, year = {2021}, date = {2021-01-01}, journal = {Expert opinion on drug discovery}, volume = {16}, number = {9}, pages = {977--989}, publisher = {Taylor & Francis}, keywords = {}, pubstate = {published}, tppubtype = {article} } |