A. L. Davies, A. Richardson, A. Børresen-dale, M. Thompson, S. S. Stratton et al., Nik-Zainal Development of methodology Nik-Zainal Acquisition of data (provided animals, acquired and managed patients, provided facilities Nik-Zainal Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis Nik-Zainal Writing, review, and/or revision of the manuscript Milestones of Lynch syndrome, Nik-Zainal Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): C.A. Purdie, S. Nik-Zainal Study supervision: S. Nik-Zainal References 1. Lynch HT, pp.1895-2015181, 2015.

W. Geurts-giele, C. Leenen, H. Dubbink, I. Meijssen, E. Post et al., Somatic aberrations of mismatch repair genes as a cause of microsatellite-unstable cancers, The Journal of Pathology, vol.32, issue.4, pp.548-59, 2014.
DOI : 10.1093/nar/gkh855

C. Bronner, S. Baker, P. Morrison, G. Warren, L. Smith et al., Mutation in the DNA mismatch repair gene homologue hMLH 1 is associated with hereditary non-polyposis colon cancer, Nature, vol.8, issue.6468, pp.258-61, 1994.
DOI : 10.1016/0016-5085(93)90368-M

I. Gazzoli, M. Loda, J. Garber, S. Syngal, and R. Kolodner, A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor, Cancer Res, vol.62, pp.3925-3933, 2002.

F. Leach, N. Nicolaides, N. Papadopoulos, B. Liu, J. J. Parsons et al., Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer, Cell, vol.75, issue.6, pp.1215-1240, 1993.
DOI : 10.1016/0092-8674(93)90330-S

M. Miyaki, M. Konishi, K. Tanaka, R. Kikuchi-yanoshita, M. Muraoka et al., Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer, Nature Genetics, vol.268, issue.3, pp.271-273, 1997.
DOI : 10.1038/382499a0

N. Nicolaides, N. Papadopoulos, B. Liu, Y. Wei, K. Carter et al., Mutations of two P/WS homologues in hereditary nonpolyposis colon cancer, Nature, vol.371, issue.6492, pp.75-80, 1994.
DOI : 10.1038/371075a0

N. Papadopoulos, N. Nicolaides, Y. Wei, S. Ruben, K. Carter et al., Mutation of a mutL homolog in hereditary colon cancer, Science, vol.263, issue.5153, pp.1625-1634, 1994.
DOI : 10.1126/science.8128251

R. Parsons, G. Li, M. Longley, P. Modrich, B. Liu et al., Mismatch repair deficiency in phenotypically normal human cells, Science, vol.67, issue.2, pp.738-778, 1995.
DOI : 10.1038/bjc.1993.40

R. Parsons, G. Li, M. Longley, W. Fang, N. Papadopoulos et al., Hypermutability and mismatch repair deficiency in RER+ tumor cells, Cell, vol.75, issue.6, pp.1227-1263, 1993.
DOI : 10.1016/0092-8674(93)90331-J

N. Llosa, M. Cruise, A. Tam, E. Wicks, E. Hechenbleikner et al., The Vigorous Immune Microenvironment of Microsatellite Instable Colon Cancer Is Balanced by Multiple Counter-Inhibitory Checkpoints, Cancer Discovery, vol.5, issue.1, pp.43-51, 2015.
DOI : 10.1158/2159-8290.CD-14-0863

J. Dudley, M. Lin, D. Le, and J. Eshleman, Microsatellite Instability as a Biomarker for PD-1 Blockade, Clinical Cancer Research, vol.22, issue.4, pp.813-833, 2016.
DOI : 10.1158/1078-0432.CCR-15-1678

V. Lee, A. Murphy, D. Le, L. Diaz, and . Jr, Mismatch Repair Deficiency and Response to Immune Checkpoint Blockade, The Oncologist, vol.21, issue.10, pp.1200-1211, 2016.
DOI : 10.1634/theoncologist.2016-0046

D. Le, J. Durham, K. Smith, H. Wang, B. Bartlett et al., Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade, Science, vol.94, issue.6349, pp.409-422, 2017.
DOI : 10.1016/0022-2836(70)90057-4

D. Le, J. Uram, H. Wang, B. Bartlett, H. Kemberling et al., PD-1 Blockade in Tumors with Mismatch-Repair Deficiency, New England Journal of Medicine, vol.372, issue.26, pp.2509-2529, 2015.
DOI : 10.1056/NEJMoa1500596

T. Schumacher and R. Schreiber, Neoantigens in cancer immunotherapy, Science, vol.43, issue.D1, pp.69-74, 2015.
DOI : 10.1093/nar/gku1075

N. Rizvi, M. Hellmann, A. Snyder, P. Kvistborg, V. Makarov et al., Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer, Science, vol.105, issue.51, pp.124-132, 2015.
DOI : 10.1073/pnas.0810114105

A. Win, N. Lindor, and M. Jenkins, Risk of breast cancer in Lynch syndrome: a systematic review, Breast Cancer Research, vol.89, issue.2, p.27, 2013.
DOI : 10.1093/jnci/89.23.1758

S. Nik-zainal, L. Alexandrov, D. Wedge, V. Loo, P. Greenman et al., Mutational Processes Molding the Genomes of 21 Breast Cancers, Cell, vol.149, issue.5, pp.979-93, 2012.
DOI : 10.1016/j.cell.2012.04.024

S. Nik-zainal, V. Loo, P. Wedge, D. Alexandrov, L. Greenman et al., The Life History of 21 Breast Cancers, Cell, vol.149, issue.5, pp.994-1007, 2012.
DOI : 10.1016/j.cell.2012.04.023

L. Alexandrov, S. Nik-zainal, D. Wedge, S. Aparicio, S. Behjati et al., Signatures of mutational processes in human cancer, Nature, vol.27, issue.7463, pp.415-436, 2013.
DOI : 10.1093/bioinformatics/btr354

L. Alexandrov, S. Nik-zainal, D. Wedge, P. Campbell, and M. Stratton, Deciphering Signatures of Mutational Processes Operative in Human Cancer, Cell Reports, vol.3, issue.1, pp.246-59, 2013.
DOI : 10.1016/j.celrep.2012.12.008

T. Helleday, S. Eshtad, and S. Nik-zainal, Mechanisms underlying mutational signatures in human cancers, Nature Reviews Genetics, vol.96, issue.9, pp.585-98, 2014.
DOI : 10.1038/nrc2998

S. Nik-zainal, H. Davies, J. Staaf, M. Ramakrishna, D. Glodzik et al., Landscape of somatic mutations in 560 breast cancer whole-genome sequences, Nature, vol.14, issue.7605, pp.47-54, 2016.
DOI : 10.1093/bioinformatics/btq170
URL : https://hal.archives-ouvertes.fr/hal-01388447

H. Davies, D. Glodzik, S. Morganella, L. Yates, J. Staaf et al., HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures, Nature Medicine, vol.58, issue.4, pp.517-542, 2017.
DOI : 10.1002/path.4325
URL : https://hal.archives-ouvertes.fr/hal-01525050

J. Auclair, D. Leroux, F. Desseigne, C. Lasset, J. Saurin et al., Novel biallelic mutations inMSH6 andPMS2 genes: gene conversion as a likely cause ofPMS2 gene inactivation, Human Mutation, vol.66, issue.11, pp.1084-90, 2007.
DOI : 10.1002/ajmg.a.30998

A. Patch, E. Christie, D. Etemadmoghadam, D. Garsed, J. George et al., Whole???genome characterization of chemoresistant ovarian cancer, Nature, vol.123, issue.7553, pp.489-94, 2015.
DOI : 10.1101/gr.129684.111

R. Hause, C. Pritchard, J. Shendure, and S. Salipante, Classification and characterization of microsatellite instability across 18 cancer types, Nature Medicine, vol.10, issue.11, pp.1342-50, 2016.
DOI : 10.1089/omi.2011.0118

S. Topalian, F. Hodi, J. Brahmer, S. Gettinger, D. Smith et al., Safety, Activity, and Immune Correlates of Anti???PD-1 Antibody in Cancer, New England Journal of Medicine, vol.366, issue.26, pp.2443-54, 2012.
DOI : 10.1056/NEJMoa1200690