Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press21510.17650/2313-805X-2019-6-2-21-27REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИClinical and genetic aspects of differential diagnostics of hereditary non-polyposis colorectal cancerКлинико-генетические аспекты дифференциальной диагностики наследственного неполипозного колоректального ракаhttps://orcid.org/0000-0001-8783-8874SemyanikhinaA. V.СемьянихинаА. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

alexandra_silina@mail.ruhttps://orcid.org/0000-0002-5565-615XRasulovA. O.РасуловА. О.
Russian Federation

Build. 1, 51 3 rd Parkovaya St., Moscow 105425

105425 Москва, ул. 3-я Парковая, 51, стр. 1

https://orcid.org/0000-0003-4775-3299LyubchenkoL. N.ЛюбченкоЛ. Н.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478; Build. 2, 8 Trubetskaya St., Moscow 119991

115478 Москва, Каширское шоссе, 24; 119991 Москва, ул. Трубецкая, 8, стр. 2

N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииN.A. Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center, Ministry of Health of RussiaНаучно-исследовательский институт урологии и интервенционной радиологии им. Н.А. Лопаткина – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииSechenov First Moscow State Medical University, Ministry of Health of RussiaФГАОУ ВО Первый Московский государственный медицинский университет им. И. М. Сеченова Минздрава России (Сеченовский университет)150520196221272707201927072019Copyright ©; 2019, Semyanikhina A.V., Rasulov A.O., Lyubchenko L.N.Copyright ©; 2019, Семьянихина А.В., Расулов А.О., Любченко Л.Н.2019Semyanikhina A.V., Rasulov A.O., Lyubchenko L.N.Семьянихина А.В., Расулов А.О., Любченко Л.Н.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/215

Lynch syndrome was synonymous with hereditary non-polyposis colorectal cancer for a long time, however, mapping of the DNA mismatch repair (MMR) genes has led to distinguish Lynch syndrome as an independent syndromic unit from a number of Lynch-like syndromes that phenotypically mimic with the most frequent hereditary variant of colon cancer but genetically representing quite a heterogeneous group. This article presents up to date clinical and genetic characteristics of Lynch syndrome and Lynch-like conditions.

Синдром Линча продолжительное время являлся синонимом наследственного неполипозного колоректального рака, однако после картирования генов системы репарации неспаренных оснований ДНК (MMR) и выделения синдрома Линча в самостоятельную единицу в группе наследственного неполипозного колоректального рака определился ряд схожих синдромов, фенотипически мимикрирующих с наиболее частым наследственным вариантом рака толстой кишки, но генетически представляющих собой гетерогенную группу. В настоящей статье описаны современные представления о клинических и генетических характеристиках синдрома Линча и подобных ему состояний.

Lynch syndromeLynch-like syndromecolorectal cancerhereditary non-polyposis colorectal cancerсиндром ЛинчаЛинч-подобный синдромнаследственный неполипозный колоректальный ракрак толстой кишкиTiwari A.K., Roy H.K., Lynch H.T. Lynch syndrome in the 21st century: clinical perspectives. QJM 2016;109(3):151–8. DOI: 10.1093/qjmed/hcv137.Lichtenstein P., Holm N.V., Verkasalo P.K. et al. Environmental and heritable factors in the causation of cancer. Analyses of cohorts of twins from Sweden, Denmark, and Finland. Engl J Med 2000;343(2):78–85. DOI: 10.1016/S0039-6257(00)00165-X.Giardiello F.M., Allen J.I., Axilbund J.E. et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US multi-society task force on colorectal cancer. Gastroenterology 2014;147(2):502–26. DOI: 10.1053/j.gastro.2014.04.001.Carethers J.M., Stoffel E.M. Lynch syndrome and Lynch syndrome mimics: the growing complex landscape of hereditary colon cancer. World J Gastroenterol 2015;21(31):9253–61. DOI: 10.3748/wjg.v21.i31.9253.Burt R. Inheritance of colorectal cancer. Drug Discov Today Dis Mech 2007;4(4): 293–300. DOI: 10.1016/j.ddmec.2008.05.004.Lynch H.T., Shaw M.W., Magnuson C.W. et al. Hereditary factors in cancer. Study of two large midwestern kindreds. Arch Intern Med 1966;117(2):206–12. DOI: 10.1001/ archinte.1966.03870080050009.Boland C.R., Troncale F.J. Familial colonic cancer without antecedent polyposis. Ann Intern Med 1984;100(5):700–1. DOI: 10.7326/0003-4819-100-5-700.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. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Genet Med 2009;11(1):35–41.Yurgelun M.B., Kulke M.H., Fuchs C.S. et al. Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol 2017;35(10):1086–95. DOI: 10.1200/ JCO.2016.71.0012.Hampel H., Frankel W., Panescu J. et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients.Cancer Res 2006;66(15):7810–7. DOI: 10.1158/0008-5472.CAN-06-1114.Kohlmann W., Gruber S.B. Lynch syndrome. Gene Reviews at GeneTests: Medical Genetics Information Resourse. University of Washington, Seattle. 1993– 2014. Available at: http://www.genetests.org.Bonadona V., Bonaïti B., Olschwang S. et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 2011;305(22): 2304–10. DOI: 10.1001/jama.2011.743. 1Jasperson K.W., Tuohy T.M., Neklason D.W., Burt R.W. Hereditary and familial colon cancer. Gastroenterology 2010;138(6): 2044–58. DOI: 10.1053/j.gastro.2010.01.054.Latham Schwark A., Srinivasan P., Kemel Y. et al. Pan-cancer microsatellite instability to predict for presence of Lynch syndrome. J Clin Oncol 2018; 36(Suppl 18):LBA1509. DOI: 10.1200/JCO.2018.36.18_suppl. LBA1509.Ballester V., Rashtak S., Boardman L. Clinical and molecular features of youngonset colorectal cancer. World J Gastroenterol 2016;22(5):1736–44. DOI: 10.3748/wjg.v22.i5.1736.Grady W.M., Markowitz S.D. The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening. Dig Dis Sci 2015;60(3):762–72. DOI: 10.1007/s10620-014-3444-4.Grady W.M., Markowitz S.D. The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening. Dig Dis Sci 2015;60(3):762–72. DOI: 10.1007/s10620-014-3444-4.Yurgelun M.B., Kastrinos F. Tumor testing for microsatellite instability to identify Lynch syndrome: new insights into an old diagnostic strategy. J Clin Oncol 2019;37(4):263–5. DOI: 10.1200/JCO.18.01664.Yurgelun M.B., Kastrinos F. Tumor testing for microsatellite instability to identify Lynch syndrome: new insights into an old diagnostic strategy. J Clin Oncol 2019;37(4):263–5. DOI: 10.1200/JCO.18.01664.https://www.nccn.org/professionals/ physician_gls/pdf/genetics_colon.pdf.Fishel R., Lescoe M.K., Rao M.R. et al. The human mutator gene homolog MSH2 and its association with hereditary nonpo lyposis colon cancer. Cell 1993;75(5):1027–38. DOI: 10.1016/0092-8674(93)90546-3.Bronner C.E., Baker S.M., Morrison P.T. et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 1994;368(6468):258–61. DOI: 10.1038/368258a0.Nicolaides N.C., Papadopoulos N., Liu B. et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 1994;371(6492):75–80. DOI: 10.1038/371075a0.Vasen H.F., Stormorken A., Menko F.H. et al. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol 2001;19(20):4074–80. DOI: 10.1200/JCO.2001.19.20.4074.Baglietto L., Lindor N.M., Dowty J.G. et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst 2010;102(3):193–201. DOI: 10.1093/jnci/djp473.Senter L., Clendenning M., Sotamaa K. et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 2008;135(2):419–28. DOI: 10.1053/j.gastro.2008.04.026.Møller P., Seppälä T., Bernstein I. et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut 2017;66(3):464–72. DOI: 10.1136/gutjnl-2015-309675.Joost P., Therkildsen C., DominguezValentin M. et al. Urinary tract cancer in Lynch syndrome; increased risk in carriers of MSH2 mutations. Urology 2015;86(6):1212–7. DOI: 10.1016/j.urology.2015.08.018.Kastrinos F., Mukherjee B., Tayob N. et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA 2009;302(16): 1790–5. DOI: 10.1001/jama.2009.1529.Vasen H.F., Watson P., Mecklin J.P., Lynch H.T. New clinical criteria for heredi tary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the In ternational Collaborative group on HNPCC. Gastroenterology 1999;116(6):1453–6. DOI: 10.1016/S0016-5085(99)70510-X.Barnetson R.A., Tenesa A., Farrington S.M. et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med 2006;354(26):2751–63. DOI: 10.1056/NEJMoa053493.Haugen A.C., Goel A., Yamada K. et al. Genetic instability caused by loss of MutS homologue 3 in human colorectal cancer. Cancer Res 2008;68(20):8465–72. DOI: 10.1158/0008-5472.CAN-08-0002.Umar A., Boland C.R, Terdiman J.P. et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004;96(4): 261–8. DOI: 10.1093/jnci/djh034.Raedle J., Trojan J., Brieger A. et al. Bethesda guidelines: relation to microsatellite instability and MLH1 promoter methylation in patients with colorectal cancer. Ann Intern Med 2001; 135(8 Pt 1):566–76. DOI: 10.7326/0003-4819-1358_Part_1-200110160-00007.http://premm.dfci.harvard.edu/.http://hnpccpredict.hgu. mrc.ac.uk/.http://www4.utsouthwestern.edu/ breasthealth/cagene/.Boland C.R. The mystery of mismatch repair deficiency: Lynch or Lynch-like? Gastroenterology 2013;144(5):868–70. DOI: 10.1053/j.gastro.2013.03.014.Antelo M., Golubicki M., Roca E. et al. Lynch-like syndrome is as frequent as Lynch syndrome in early-onset nonfamilial non-polyposis colorectal cancer. Int J Cancer 2019. DOI: 10.1002/ijc.32160.Haraldsdottir S., Hampel H., Tomsic J. et al. Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology 2014;147(6):1308–16e1. DOI: 10.1053/j.gastro.2014.08.041.Geurts-Giele W.R., Leenen C.H., Dubbink H.J. et al. Somatic aberrations of mismatch repair genes as a cause of microsatellite-unstable cancers. J Pathol 2014; 234(4):548–59. DOI: 10.1002/path.4419.Durno C.A., Sherman P.M., Aronson M. et al. Phenotypic and genotypic characterisation of biallelic mismatch repair deficiency (BMMR-D) syndrome. Eur J Cancer 2015;51(8):977–83. DOI: 10.1016/j.ejca.2015.02.008.Bakry D., Aronson M., Durno C. Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium. Eur J Cancer 2014;50(5):987–96. DOI: 10.1016/j.ejca.2013.12.005.Durno C.A., Holter S., Sherman P.M., Gallinger S. The gastrointestinal phenotype of germline biallelic mismatch repair gene mutations. Am J Gastroenterol 2010;105(11):2449–56. DOI: 10.1038/ajg.2010.215.Durno C.A. Colonic polyps in children and adolescents. Can J Gastroenterol 2007; 21(4):233–9. DOI: 10.1155/2007/401674.Herkert J.C., Niessen R.C., OlderodeBerends M.J. et al. Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines. Eur J Cancer 2011;47(7):965–82. DOI: 10.1016/j.ejca.2011.01.013.Turcot J., Despres J.P., Pierre F. Malignant tumors of the central nervous system associ ated with familial polyposis of the colon: report of two cases. Dis Colon Rectum 1959;2:465–8. DOI: 10.1007/BF02616938.Paraf F., Jothy S., Van Meir E.G. Brain tumor-polyposis syndrome: two genetic diseases? J Clin Oncol 1997;15:2744–58. DOI: 10.1200/JCO.1997.15.7.2744.Palles C., Cazier J.B., Howarth K.M. et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 2013;45(2): 136–44. DOI: 10.1038/ng.2503.Zetner D.B., Bisgaard M.L. Familial colorectal cancer type X. Curr Genomics 2017;18(4):341–59. DOI: 10.2174/ 1389202918666170307161643.Lindor N.M., Rabe K., Petersen G.M. et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA 2005;293(16):1979–85. DOI: 10.1001/jama.293.16.1979.