Identification of a novel MSH6 germline variant in a family with multiple gastro-intestinal malignancies by next generation sequencing

详细信息    查看全文

• 作者：Ashton A. Connor (1) (2) (3) (4)
  Hagit Katzov-Eckert (1)
  Thomas Whelan (1)
  Melyssa Aronson (1) (5)
  Lynette Lau (6)
  Christian Marshall (6) (7)
  George S. Charames (8) (9)
  Aaron Pollett (8) (9)
  Steven Gallinger (1) (2) (3) (4) (5)
  Jordan Lerner-Ellis (4) (8) (9)
  
  1. Lunenfeld-Tanenbaum Research Institute ; Mount Sinai Hospital ; Toronto ; ON ; Canada
  2. Institute of Medical Science ; University of Toronto ; Toronto ; ON ; Canada
  3. Division of General Surgery ; Department of Surgery ; University of Toronto ; Toronto ; ON ; Canada
  4. Ontario Institute for Cancer Research ; Toronto ; ON ; Canada
  5. Zane Cohen Centre for Digestive Diseases ; Mount Sinai Hospital ; Toronto ; ON ; Canada
  6. The Centre for Applied Genomics ; The Hospital for Sick Children ; Peter Gilgan Centre for Research and Learning ; Toronto ; ON ; Canada
  7. The McLaughlin Centre ; University of Toronto ; Toronto ; ON ; Canada
  8. Department of Laboratory Medicine and Pathobiology ; University of Toronto ; Toronto ; ON ; Canada
  9. Department of Pathology and Laboratory Medicine ; Mount Sinai Hospital ; Toronto ; ON ; Canada
  
• 关键词：Gastrointestinal cancer ; DNA mismatch repair ; MSH6 ; Next generation sequencing ; Clinical genomics
• 刊名：Familial Cancer
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：14
• 期：1
• 页码：69-75
• 全文大小：614 KB
• 参考文献：1. Al-Sukhni, W, Aronson, M, Gallinger, S (2008) Hereditary colorectal cancer syndromes: familial adenomatous polyposis and lynch syndrome. Surg Clin North Am 88: pp. 819-844 CrossRef
  2. Shia, J (2008) Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn 10: pp. 293-300 CrossRef
  3. Zhang, L (2008) Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part II. The utility of microsatellite instability testing. J Mol Diagn 10: pp. 301-307 CrossRef
  Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med 11: pp. 35-41 CrossRef
  4. Cicek, MS, Lindor, NM, Gallinger, S, Bapat, B, Hopper, JL, Jenkins, MA, Young, J, Buchanan, D, Walsh, MD, Marchand, L, Burnett, T, Newcomb, PA, Grady, WM, Haile, RW, Casey, G, Plummer, SJ, Krumroy, LA, Baron, JA, Thibodeau, SN (2011) Quality assessment and correlation of microsatellite instability and immunohistochemical markers among population- and clinic-based colorectal tumors results from the Colon Cancer Family Registry. J Mol Diagn 13: pp. 271-281 CrossRef
  5. Moreira, L, Balaguer, F, Lindor, N, Chapelle, A, Hampel, H, Aaltonen, LA, Hopper, JL, Le Marchand, L, Gallinger, S, Newcomb, PA, Haile, R, Thibodeau, SN, Gunawardena, S, Jenkins, MA, Buchanan, DD, Potter, JD, Baron, JA, Ahnen, DJ, Moreno, V, Andreu, M, Ponz de Leon, M, Rustgi, AK, Castells, A (2012) Identification of Lynch syndrome among patients with colorectal cancer. JAMA 308: pp. 1555-1565 CrossRef
  6. Tanskanen, T, Gylfe, AE, Katainen, R, Taipale, M, Renkonen-Sinisalo, L, Mecklin, JP, J盲rvinen, H, Tuupanen, S, Kilpivaara, O, Vahteristo, P, Aaltonen, LA (2013) Exome sequencing in diagnostic evaluation of colorectal cancer predisposition in young patients. Scand J Gastroenterol 48: pp. 672-678 CrossRef
  7. Link, DC, Schuettpelz, LG, Shen, D, Wang, J, Walter, MJ, Kulkarni, S, Payton, JE, Ivanovich, J, Goodfellow, PJ, Beau, M, Koboldt, DC, Dooling, DJ, Fulton, RS, Bender, RH, Fulton, LL, Delehaunty, KD, Fronick, CC, Appelbaum, EL, Schmidt, H, Abbott, R, O鈥橪aughlin, M, Chen, K, McLellan, MD, Varghese, N, Nagarajan, R, Heath, S, Graubert, TA, Ding, L, Ley, TJ, Zambetti, GP, Wilson, RK, Mardis, ER (2011) Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA 305: pp. 1568-1576 CrossRef
  8. Pritchard, CC, Smith, C, Salipante, SJ, Lee, MK, Thornton, AM, Nord, AS, Gulden, C, Kupfer, SS, Swisher, EM, Bennett, RL, Novetsky, AP, Jarvik, GP, Olopade, OI, Goodfellow, PJ, King, MC, Tait, JF, Walsh, T (2012) ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 14: pp. 357-366 CrossRef
  9. Yang, Y, Muzny, DM, Reid, JG, Bainbridge, MN, Willis, A, Ward, PA, Braxton, A, Beuten, J, Xia, F, Niu, Z, Hardison, M, Person, R, Bekheirnia, MR, Leduc, MS, Kirby, A, Pham, P, Scull, J, Wang, M, Ding, Y, Plon, SE, Lupski, JR, Beaudet, AL, Gibbs, RA, Eng, CM (2013) Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 369: pp. 1502-1511 CrossRef
  10. Jacob, HJ (2013) Next-generation sequencing for clinical diagnostics. N Engl J Med 369: pp. 1557-1558 CrossRef
  11. Cotterchio, M, McKeown-Eyssen, G, Sutherland, H, Buchan, G, Aronson, M, Easson, AM, Macey, J, Holowaty, E, Gallinger, S (2000) Ontario familial colon cancer registry: methods and first-year response rates. Chronic Dis Can 21: pp. 81-86
  12. Li, H, Durbin, R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: pp. 1754-1760 CrossRef
  13. McKenna, A, Hanna, M, Banks, E, Sivachenko, A, Cibulskis, K, Kernytsky, A, Garimella, K, Altshuler, D, Gabriel, S, Daly, M, DePristo, MA (2010) The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: pp. 1297-1303 CrossRef
  14. Wang, K, Li, M, Hakonarson, H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38: pp. e164 CrossRef
  15. Jiang, YH, Yuen, RK, Jin, X, Wang, M, Chen, N, Wu, X, Ju, J, Mei, J, Shi, Y, He, M, Wang, G, Liang, J, Wang, Z, Cao, D, Carter, MT, Chrysler, C, Drmic, IE, Howe, JL, Lau, L, Marshall, CR, Merico, D, Nalpathamkalam, T, Thiruvahindrapuram, B, Thompson, A, Uddin, M, Walker, S, Luo, J, Anagnostou, E, Zwaigenbaum, L, Ring, RH, Wang, J, Lajonchere, C, Wang, J, Shih, A, Szatmari, P, Yang, H, Dawson, G, Li, Y, Scherer, SW (2013) Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. Am J Hum Genet 93: pp. 249-263 CrossRef
  16. Rehm, HL (2013) Disease-targeted sequencing: a cornerstone in the clinic. Nat Rev Genet 14: pp. 295-300 CrossRef
  17. Thompson, BA, Spurdle, AB, Plazzer, JP, Greenblatt, MS, Akagi, K, Al-Mulla, F, Bapat, B, Bernstein, I, Capell谩, G, Dunnen, JT, Sart, D, Fabre, A, Farrell, MP, Farrington, SM, Frayling, IM, Frebourg, T, Goldgar, DE, Heinen, CD, Holinski-Feder, E, Kohonen-Corish, M, Robinson, KL, Leung, SY, Martins, A, Moller, P, Morak, M, Nystrom, M, Peltomaki, P, Pineda, M, Qi, M, Ramesar, R, Rasmussen, LJ, Royer-Pokora, B, Scott, RJ, Sijmons, R, Tavtigian, SV, Tops, CM, Weber, T, Wijnen, J, Woods, MO, Macrae, F, Genuardi, M (2014) Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nat Genet 46: pp. 107-115 CrossRef
  18. Richards, CS, Bale, S, Bellissimo, DB, Das, S, Grody, WW, Hegde, MR, Lyon, E, Ward, BE (2008) ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med 10: pp. 294-300 CrossRef
  19. Baglietto, L, Lindor, NM, Dowty, JG, White, DM, Wagner, A, Gomez Garcia, EB, Vriends, AH, Cartwright, NR, Barnetson, RA, Farrington, SM, Tenesa, A, Hampel, H, Buchanan, D, Arnold, S, Young, J, Walsh, MD, Jass, J, Macrae, F, Antill, Y, Winship, IM, Giles, GG, Goldblatt, J, Parry, S, Suthers, G, Leggett, B, Butz, M, Aronson, M, Poynter, JN, Baron, JA, Le Marchand, L, Haile, R, Gallinger, S, Hopper, JL, Potter, J, Chapelle, A, Vasen, HF, Dunlop, MG, Thibodeau, SN, Jenkins, MA (2010) Risks of lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst 102: pp. 193-201 CrossRef
  20. Schulmann, K, Brasch, FE, Kunstmann, E, Engel, C, Pagenstecher, C, Vogelsang, H, Kr眉ger, S, Vogel, T, Knaebel, HP, R眉schoff, J, Hahn, SA, Knebel-Doeberitz, MV, Moeslein, G, Meltzer, SJ, Schackert, HK, Tympner, C, Mangold, E, Schmiegel, W (2005) HNPCC-associated small bowel cancer: clinical and molecular characteristics. Gastroenterology 128: pp. 590-599 CrossRef
  21. Watson, P, Vasen, HF, Mecklin, JP, Bernstein, I, Aarnio, M, J盲rvinen, HJ, Myrh酶j, T, Sunde, L, Wijnen, JT, Lynch, HT (2008) The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 123: pp. 444-449 CrossRef
  22. Church, J, Simmang, C (2003) Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer). Dis Colon Rectum 46: pp. 1001-1012 CrossRef
  23. Ribic, CM, Sargent, DJ, Moore, MJ, Thibodeau, SN, French, AJ, Goldberg, RM, Hamilton, SR, Laurent-Puig, P, Gryfe, R, Shepherd, LE, Tu, D, Redston, M, Gallinger, S (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349: pp. 247-257 CrossRef
  24. Sargent, DJ, Marsoni, S, Monges, G, Thibodeau, SN, Labianca, R, Hamilton, SR, French, AJ, Kabat, B, Foster, NR, Torri, V, Ribic, C, Grothey, A, Moore, M, Zaniboni, A, Seitz, JF, Sinicrope, F, Gallinger, S (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28: pp. 3219-3226 CrossRef
  25. Fallik, D, Borrini, F, Boige, V, Viguier, J, Jacob, S, Miquel, C, Sabourin, JC, Ducreux, M, Praz, F (2003) Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res 63: pp. 5738-5744
  26. Win, AK, Jenkins, MA, Buchanan, DD, Clendenning, M, Young, JP, Giles, GG, Goldblatt, J, Leggett, BA, Hopper, JL, Thibodeau, SN, Lindor, NM (2011) Determining the frequency of de novo germline mutations in DNA mismatch repair genes. J Med Genet 48: pp. 530-534 CrossRef
  27. Hegde, M, Ferber, M, Mao, R, Samowitz, W, Ganguly, A (2014) ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis). Genet Med 16: pp. 101-116 CrossRef
  28. Dub茅, C, Rostom, A, Lewin, G, Tsertsvadze, A, Barrowman, N, Code, C, Sampson, M, Moher, D (2007) The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 146: pp. 365-375 CrossRef
  29. Johnston, JJ, Rubinstein, WS, Facio, FM, Ng, D, Singh, LN, Teer, JK, Mullikin, JC, Biesecker, LG (2012) Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. Am J Hum Genet 91: pp. 97-108 CrossRef
  30. Dewey, FE, Grove, ME, Pan, C, Goldstein, BA, Bernstein, JA, Chaib, H, Merker, JD, Goldfeder, RL, Enns, GM, David, SP, Pakdaman, N, Ormond, KE, Caleshu, C, Kingham, K, Klein, TE, Whirl-Carrillo, M, Sakamoto, K, Wheeler, MT, Butte, AJ, Ford, JM, Boxer, L, Ioannidis, JP, Yeung, AC, Altman, RB, Assimes, TL, Snyder, M, Ashley, EA, Quertermous, T (2014) Clinical interpretation and implications of whole-genome sequencing. JAMA 311: pp. 1035-1045 CrossRef
  31. Green, RC, Berg, JS, Grody, WW, Kalia, SS, Korf, BR, Martin, CL, McGuire, AL, Nussbaum, RL, O鈥橠aniel, JM, Ormond, KE, Rehm, HL, Watson, MS, Williams, MS, Biesecker, LG (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 15: pp. 565-574 CrossRef
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Human Genetics
  Epidemiology
  
• 出版者：Springer Netherlands
• ISSN：1573-7292

文摘

The identification of germline variants that predispose to cancer is important to further our understanding of tumorigenesis, guide patient management, prevent disease in unaffected relatives, and inform best practice for health care. We describe a kindred with multiple gastrointestinal malignancies where a novel MSH6 germline susceptibility variant was identified by exome sequencing after eluding serial routine testing in multiple affected members. This case fosters discussion of our current understanding of DNA mismatch repair deficiency, the management of Lynch Syndrome, and the emerging role of next generation sequencing in laboratory medicine to identify rare pathogenic germline variants in a comprehensive, unbiased fashion.