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World Journal of Surgical Oncology

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Open Access 01-09-2023 | Rectal Cancer | Case Report

A unique case of rectal cancer with coexistence of multiple pathways of carcinogenesis

Authors: Nisha Rateria, Ritu Ojha, Mridula Shukla, Manoj Pandey

Published in: World Journal of Surgical Oncology | Issue 1/2023

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.

Sung H, Ferlay J, Seigel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRefPubMed

Grady WM. Genomic instability and colon cancer. Cancer Metastasis Rev. 2004;23:11–27.CrossRefPubMed

Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61(5):759–67.CrossRefPubMed

Lynch HT, Snyder CL, Shaw TG, Heinen CD, Hitchins MP. Milestones of Lynch syndrome: 1895–2015. Nat Rev Cancer. 2015;15(3):181–94.CrossRefPubMed

Loeb LA. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991;51:3075–9.PubMed

Rajagopalan H, Lengauer C. Aneuploidy and cancer. Nature. 2004;432:338–41.CrossRefPubMed

Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW. Activation of β-catenin-Tcf signalling in colon cancer by mutations in β-catenin or APC. Science. 1997;275(5307):1787–90.CrossRefPubMed

Smith G, Carey FA, Beattie J, Wilkie MJ, Lightfoot TJ, Coxhead J. Mutations in APC, Kirsten-ras and p53 -alternative genetic pathways to colorectal cancer. Proc Natl Acad Sci USA. 2002;99:9433–8.CrossRefPubMedPubMedCentral

Peltoma ki P, Vasen H. Mutations associated with HNPCC predisposition—update of ICG-HNPCC/INSIGHT mutation database. Dis Markers. 2004;20:269–76.

10.

Baglietto L, Lindor NM, Dowty JG, et al. Risks of Lynch syndrome cancer for MSH6 mutation carriers. J Natl Cancer Inst. 2009;102:193–201.CrossRefPubMed

11.

Acharya S, Wilson T, Gradia S, et al. hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc Natl Acad Sci USA. 1996;93:13629–34.CrossRefPubMedPubMedCentral

12.

Ibrahim AE, Arends MJ. Molecular typing of colorectal cancer: applications in diagnosis and treatment. Diagn Histopathol. 2012;18(2):70–80.CrossRef

13.

Wang Q, Lasset C, Desseigne F, Saurin JC, Maugard C, Navarro C, Ruano E, Descos L, Trillet-Lenoir V, Bosset JF, Puisieux A. Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with non polyposis colorectal cancer 1998. Hum Genet. 1999;105(1–2):79–85.PubMed

14.

Liu T, Yan H, Kuismanen S, Percesepe A, Bisgaard ML, Pedroni M, Benatti P, Kinzler KW, Vogelstein B, Ponz de Leon M, Peltomäki P, Lindblom A. The role of hPMS1 and hPMS2 in predisposing to colorectal cancer. Cancer Res. 2001;61(21):7798–802.

15.

Cassone M, Salehi LB, Tedaldi G, Tebaldi M, Zampiga V, Biancolella M, Testa B, Calistri D, Mastrogiorgio G, Lanciotti S, D’Apice MR, Novelli G, Sangiuolo F. Coexistence of two novel mutations in CDKN2A and PMS1 genes in a single patient identifies a new and severe cancer predisposition syndrome. Oncomedicine. 2017;2:88–92.CrossRef

16.

Arulananda S, Thapa B, Walkiewicz M, et al. Mismatch repair protein defects and microsatellite instability in malignant pleural mesothelioma. J Thorac Oncol. 2018;13(10):1588–94.CrossRefPubMed

17.

Schiemann U, Koch YM, Gross M, Daum J, Lohse P, Baretton G, Muders M, Mussack T, Kopp R, Federb EH. Extended microsatellite analysis in microsatellite stable, MSH2 and MLH1 mutation-negative HNPCC patients: genetic reclassification and correlation with clinical features. Digestion. 2004;69:166–76.CrossRefPubMed

18.

Wu Y, Berends MJ, Mensink RG, et al. Association of hereditary non polyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. Am J Hum Genet. 1999;65:1291–8.CrossRefPubMedPubMedCentral

19.

Berends MJ, Wu Y, Sijmons RH, et al. Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet. 2002;70:26–37.CrossRefPubMed

20.

Plaschke J, Engel C, Kruger S, et al. 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.CrossRefPubMed

Title: A unique case of rectal cancer with coexistence of multiple pathways of carcinogenesis
Authors: Nisha Rateria
Ritu Ojha
Mridula Shukla
Manoj Pandey
Publication date: 01-09-2023
Publisher: BioMed Central
Keywords: Rectal Cancer
Molecular Genetics
Gastrointestinal Cancer
Published in: World Journal of Surgical Oncology / Issue 1/2023
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/s12957-023-03157-9

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Abstract

Background

Case presentation

Conclusions

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