A Unique Case of Rectal Cancer with Coexistence of Multiple Pathways of Carcinogenesis

Overview

Journal World J Surg Oncol

Publisher Biomed Central

Specialties General Surgery
Oncology

Date 2023 Sep 1

PMID 37658412

Authors

Nisha Rateria

Ritu Ojha

Mridula Shukla

Manoj Pandey

Affiliations

Soon will be listed here.

Abstract

Background: Colorectal cancer with a global incidence of 10% has multiple pathways implicated in its carcinogenesis. WNT signaling is the principal underlying pathway via APC gene, while defective mismatch repair genes and epigenetic changes also are known to contribute.

Case Presentation: Here, we present an unusual case of rectal adenocarcinoma in a woman, with germline MSH6 and PMS1 mutations, and simultaneous somatic APC and TP53 mutations treated with surgery and adjuvant capecitabine.

Conclusions: The case is unique suggesting a possible interaction between the two pathways and contributing to carcinogenesis in this patient. This also suggests need for a thorough germline and somatic mutation evaluation in select colorectal cancer patients to direct a tailored therapy.

References

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Grady W . Genomic instability and colon cancer. Cancer Metastasis Rev. 2004; 23(1-2):11-27. DOI: 10.1023/a:1025861527711. View

Fearon E, Vogelstein B . A genetic model for colorectal tumorigenesis. Cell. 1990; 61(5):759-67. DOI: 10.1016/0092-8674(90)90186-i. View

Lynch H, Snyder C, Shaw T, Heinen C, Hitchins M . Milestones of Lynch syndrome: 1895-2015. Nat Rev Cancer. 2015; 15(3):181-94. DOI: 10.1038/nrc3878. View

Loeb L . Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991; 51(12):3075-9. View

Rajagopalan H, Lengauer C . Aneuploidy and cancer. Nature. 2004; 432(7015):338-41. DOI: 10.1038/nature03099. View

Morin P, Sparks A, Korinek V, Barker N, Clevers H, Vogelstein B . Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997; 275(5307):1787-90. DOI: 10.1126/science.275.5307.1787. View

Smith G, Carey F, Beattie J, Wilkie M, Lightfoot T, Coxhead J . Mutations in APC, Kirsten-ras, and p53--alternative genetic pathways to colorectal cancer. Proc Natl Acad Sci U S A. 2002; 99(14):9433-8. PMC: 123158. DOI: 10.1073/pnas.122612899. View

Baglietto L, Lindor N, Dowty J, White D, Wagner A, Gomez Garcia E . Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2009; 102(3):193-201. PMC: 2815724. DOI: 10.1093/jnci/djp473. View

10.

Acharya S, Wilson T, Gradia S, Kane M, Guerrette S, Marsischky G . hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc Natl Acad Sci U S A. 1996; 93(24):13629-34. PMC: 19374. DOI: 10.1073/pnas.93.24.13629. View

11.

Wang Q, Lasset C, Desseigne F, Saurin J, Maugard C, Navarro C . Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer. Hum Genet. 1999; 105(1-2):79-85. DOI: 10.1007/s004399900064. View

12.

Arulananda S, Thapa B, Walkiewicz M, Zapparoli G, Williams D, Dobrovic A . Mismatch Repair Protein Defects and Microsatellite Instability in Malignant Pleural Mesothelioma. J Thorac Oncol. 2018; 13(10):1588-1594. DOI: 10.1016/j.jtho.2018.07.015. View

13.

Schiemann U, Muller-Koch Y, Gross M, Daum J, Lohse P, Baretton G . Extended microsatellite analysis in microsatellite stable, MSH2 and MLH1 mutation-negative HNPCC patients: genetic reclassification and correlation with clinical features. Digestion. 2004; 69(3):166-76. DOI: 10.1159/000078223. View

14.

Wu Y, Berends M, Mensink R, Kempinga C, Sijmons R, van der Zee A . Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. Am J Hum Genet. 1999; 65(5):1291-8. PMC: 1288281. DOI: 10.1086/302612. View

15.

Berends M, Wu Y, Sijmons R, Mensink R, van der Sluis T, Hordijk-Hos J . Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet. 2001; 70(1):26-37. PMC: 384896. DOI: 10.1086/337944. View

16.

Plaschke J, Engel C, Kruger S, Holinski-Feder E, Pagenstecher C, Mangold E . Lower incidence of colorectal cancer and later age of disease onset in 27 families with pathogenic MSH6 germline mutations compared with families with MLH1 or MSH2 mutations: the German Hereditary Nonpolyposis Colorectal Cancer Consortium. J Clin Oncol. 2004; 22(22):4486-94. DOI: 10.1200/JCO.2004.02.033. View