Keywords
How to Cite
Abstract
Breast cancer (BC) is not a typical manifestation of Lynch syndrome. The existence and extent of excessive breast cancer risk in carriers of pathogenic mutations in the Lynch syndrome-associated genes (MLH1, MSH2, MSH6, PMS2) remains an open question. In addition, it is known that some of the breast neoplasms in patients with this syndrome are causally linked to the hereditary mutation, and some arise completely independently of the hereditary defect in the gene of the DNA mismatch repair system. In the case of accidental detection of such germline mutations in breast cancer patients, a thorough differential diagnosis between these categories of tumors is required, and the result of it is actionable, requiring changes in the management. This is a report of a case of breast cancer that arose in a carrier of a pathogenic mutation in the PMS2 gene, which was an accidental finding. The description of molecular genetic diagnostics is given: the microsatellite markers assessment and the detection of «loss of heterozygosity» allowed to classify the neoplasm in a category of cases that developed without any causal link to the patient's Lynch syndrome.
References
Roberts ME, Jackson SA, Susswein LR et al. MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer // Genet Med. 2018;20(10):1167–1174. https: // doi: 10.1038/gim.2017.254
Nikitin AG, Chudakova DA, Enikeev RF et al. Lynch Syndrome Germline Mutations in Breast Cancer: Next Generation Sequencing Case-Control Study of 1,263 Participants // Front Oncol. 2020;10):666. https: // doi: 10.3389/fonc.2020.00666
Nguyen-Dumont T, Steen JA, Winship I et al. Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer // Fam Cancer. 2020;19(3):197–202. https: // doi: 10.1007/s10689-020-00164-7
Wang X, Brzosowicz JP, Park JY. Response to Roberts et al. 2018: cohort ascertainment and methods of analysis impact the association between cancer and genetic predisposition — the tale of breast cancer risk and Lynch syndrome genes MSH6/PMS2. Genet Med. 2019 Sep;21(9):2156–2157. https: // doi: 10.1038/s41436-019-0471-8. Epub 2019 Feb 28
Win AK, Jenkins MA, Dowty JG et al. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer // Cancer Epidemiol Biomarkers Prev. 2017;26(3):404–412. https: // doi: 10.1158/1055-9965.EPI-16-0693
Ten Broeke SW, van der Klift HM, Tops CMJ et al. Cancer Risks for PMS2-Associated Lynch Syndrome // J Clin Oncol. 2018;36(29):2961–2968. https: // doi: 10.1200/JCO.2018.78.4777
Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis // Nature. 1993;363(6429):558-561. https: // doi: 10.1038/363558a0
Buhard O, Suraweera N, Lectard A, Duval A, Hamelin R. Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis // Dis Markers. 2004;20(4–5):251–257. https: // doi: 10.1155/2004/159347
Ten Broeke SW, van Bavel TC, Jansen AML et al. Molecular Background of Colorectal Tumors From Patients With Lynch Syndrome Associated With Germline Variants in PMS2 // Gastroenterology. 2018;155(3):844–851. https: // doi: 10.1053/j.gastro.2018.05.020
Loughrey MB, McGrath J, Coleman HG et al. Identifying mismatch repair-deficient colon cancer: near-perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series // Histopathology. 2020. https: // doi: 10.1111/his.14233
Walsh MD, Buchanan DD, Cummings MC et al. Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry // Clin Cancer Res. 2010;16(7):2214–2224. https: // doi: 10.1158/1078-0432.CCR-09-3058
Lotsari JE, Gylling A, Abdel-Rahman WM et al. Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases // Breast Cancer Res. 2012;14(3):R90. https: // doi: 10.1186/bcr3205
Porkka NK, Olkinuora A, Kuopio T et al. Does breast carcinoma belong to the Lynch syndrome tumor spectrum? — Somatic mutational profiles vs. ovarian and colorectal carcinomas // Oncotarget. 2020;11(14):1244–1256. https: // doi: 10.18632/oncotarget.27538
Luchini C, Bibeau F, Ligtenberg MJL et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach // Ann Oncol. 2019;30(8):1232–1243. https: // doi: 10.1093/annonc/mdz116
Wen YH, Brogi E, Zeng Z et al. DNA mismatch repair deficiency in breast carcinoma: a pilot study of triple-negative and non-triple-negative tumors // Am J Surg Pathol. 2012;36(11):1700–1708. https: // doi: 10.1097/PAS.0b013e3182627787
Beggs AD, Kousparos G, Hodgson SV. Loss of mismatch repair protein expression in breast carcinoma in patients with Lynch Syndrome: report of two cases // Breast J. 2013;19(2):193–195. https: // doi: 10.1111/tbj.12077
Sorscher S. The Importance of Distinguishing Sporadic Cancers from Those Related to Cancer Predisposing Germline Mutations // Oncologist. 2018;23(11):1266–1268. https: // doi: 10.1634/theoncologist.2017-0681
D'Arcy C, Wen YH, Stadler ZK, Brogi E, Shia J. Synchronous breast cancers with different morphologic and molecular phenotypes occurring in Lynch syndrome: what does the heterogeneity imply? // Am J Surg Pathol. 2011;35(11):1743-1748. https: // doi: 10.1097/PAS.0b013e3182320cff
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2021