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CC BY 4.0 · Glob Med Genet 2023; 10(01): 001-005
DOI: 10.1055/s-0042-1759888
Original Article

PMS2 Pathogenic Variant in Lynch Syndrome-Associated Colorectal Cancer with Polyps

Henriette Poaty
1   Embryology and Genetic Laboratory, Faculty of Health Sciences, Marien Ngouabi University, Brazzaville, Congo
2   Department of Clinical Sciences, Institute of Research on Health Sciences, Brazzaville, Congo
,
Lauria Batamba Bouya
1   Embryology and Genetic Laboratory, Faculty of Health Sciences, Marien Ngouabi University, Brazzaville, Congo
,
Aimé Lumaka
3   Centre de Génétique de l'Université de Kinshasa, DR Congo
4   Service de Génétique Humaine, Sart Tilman, Avenue de l'Hôpital 13, 4000, Liège, Belgium
,
Arnaud Mongo-Onkouo
1   Embryology and Genetic Laboratory, Faculty of Health Sciences, Marien Ngouabi University, Brazzaville, Congo
5   Gastro-Enterology and Internal Medicine Service, CHU Brazzaville, Congo
,
Deby Gassaye
1   Embryology and Genetic Laboratory, Faculty of Health Sciences, Marien Ngouabi University, Brazzaville, Congo
5   Gastro-Enterology and Internal Medicine Service, CHU Brazzaville, Congo
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Abstract

Background Lynch syndrome (LS) is an autosomal dominant condition due to the germline mutation in the mismatch repair (MMR) genes including MLH1, MSH2, MSH6, and PMS2 (post-meiotic segregation increased 2). The MMR mutation carriers have high risk for cancers. Pathogenic PMS2 variants are rarely reported in LS-associated colorectal cancer (CRC) with colorectal polyps. The aim of the study was to investigate the genetic etiology of CRC in an individual with CRC with multiple colorectal polyps and a family history of cancers.

Patients and Methods The index patient was an African male affected by CRC with multiple colorectal polyps. The clinical diagnostic for LS was based on the Amsterdam II criteria and pedigree. Next-generation sequencing with inherited cancer genes panel was used to detect the pathogenic variant.

Results The patient fulfilled the Amsterdam II criteria and the pedigree revealed a family history of recurrent CRC. A deleterious PMS2 germline heterozygous mutation c.2192_2196delTAACT was detected.

Conclusion Our study supports the notion that LS may be associated with polyps and shows the predisposition of PMS2 heterozygous mutation in LS-associated CRC at young age.

Keywords

lynch syndrome - PMS2 deficiency - mismatch repair gene - colorectal cancer

Authors' Contributions

H.P. and D.G. designed the study. L.B.B., A.L., D.G., and H.P. performed the research and analyzed the data. A.M.-O. contributed materials and tools. H.P. and A.L. wrote the paper. All authors contributed and approved the final manuscript.


Ethic Approval and Consent to Participate

Not applicable.


Consent for Publication

Obtained.


Availability of Data and Material

Not applicable.




Publication History

Received: 02 September 2022

Accepted: 25 October 2022

Article published online:
11 January 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Lepore Signorile M, Disciglio V, Di Carlo G, Pisani A, Simone C, Ingravallo G. From genetics to histomolecular characterization: an insight into colorectal carcinogenesis in Lynch syndrome. Int J Mol Sci 2021; 22 (13) 6767
    CrossrefPubMedGoogle Scholar
  • 2 Bucksch K, Zachariae S, Aretz S. et al; German Consortium for Familial Intestinal Cancer. Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study. BMC Cancer 2020; 20 (01) 460
    CrossrefPubMedGoogle Scholar
  • 3 Rosenblum RE, Ang C, Suckiel SA. et al. Lynch syndrome-associated variants and cancer rates in an ancestrally diverse biobank. JCO Precis Oncol 2020; 4 (04) 1429-1444
    CrossrefPubMedGoogle Scholar
  • 4 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
    CrossrefPubMedGoogle Scholar
  • 5 Bernstedt SW, Björk J, Fritzell K, Spigelman AD, Björck E, Backman AS. Room for improvement: one third of Lynch syndrome patients presenting for genetic testing in a highly specialised centre in Stockholm already have cancer. Hered Cancer Clin Pract 2021; 19 (01) 18
    CrossrefPubMedGoogle Scholar
  • 6 Poaty H, Aba Gandzion C, Soubeyran I. et al. The identification of Lynch syndrome in Congolese colorectal cancer patients. Bull Cancer 2017; 104 (10) 831-839
    CrossrefPubMedGoogle Scholar
  • 7 Niessen RC, Kleibeuker JH, Westers H. et al. PMS2 involvement in patients suspected of Lynch syndrome. Genes Chromosomes Cancer 2009; 48 (04) 322-329
    CrossrefPubMedGoogle Scholar
  • 8 Senter L, Clendenning M, Sotamaa K. et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 2008; 135 (02) 419-428
    CrossrefPubMedGoogle Scholar
  • 9 Ramchander NC, Ryan NAJ, Crosbie EJ, Evans DG. Homozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD). BMC Med Genet 2017; 18 (01) 40
    CrossrefPubMedGoogle Scholar
  • 10 Poaty H, Batamba Bouya L, Ondima IPL. et al. BMPR1A and SMAD4 mutations in juvenile polyposis syndrome: clinicopathological and genetic data from two congolese patients. Gene Rep 2021; 23: 101141
    CrossrefGoogle Scholar
  • 11 Blount J, Prakash A. The changing landscape of Lynch syndrome due to PMS2 mutations. Clin Genet 2018; 94 (01) 61-69
    CrossrefPubMedGoogle Scholar
  • 12 Zhu F, Pan D, Zhang H, Ye Q, Xu P, Pan J. Single-center study of Lynch syndrome screening in colorectal polyps. Hered Cancer Clin Pract 2019; 17: 9
    CrossrefPubMedGoogle Scholar
  • 13 Burt RW. Colonic polyps in lynch syndrome. Dis Colon Rectum 2015; 58 (04) 371-372
    CrossrefPubMedGoogle Scholar
  • 14 Eleftheriadis N, Inoue H, Ikeda H, Onimaru M, Maselli R, Kudo SE. Polyps in Lynch syndrome. Differences in quality of colonoscopy between Western and Eastern endoscopists. Endoscopy 2015; 47 (01) 89
    PubMedGoogle Scholar
  • 15 Guindalini RS, Win AK, Gulden C. et al. Mutation spectrum and risk of colorectal cancer in African American families with Lynch syndrome. Gastroenterology 2015; 149 (06) 1446-1453
    CrossrefPubMedGoogle Scholar
  • 16 Talseth-Palmer BA, McPhillips M, Groombridge C, Spigelman A, Scott RJ. MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer. Hered Cancer Clin Pract 2010; 8 (01) 5
    CrossrefPubMedGoogle Scholar
  • 17 Worthley DL, Walsh MD, Barker M. et al. Familial mutations in PMS2 can cause autosomal dominant hereditary nonpolyposis colorectal cancer. Gastroenterology 2005; 128 (05) 1431-1436
    CrossrefPubMedGoogle Scholar
  • 18 Wang Q, Leclerc J, Bougeard G. et al; French Consortium of Oncogenetic laboratories for colorectal cancers, Unicancer Cancer Genetic Group (GGC). Characterisation of heterozygous PMS2 variants in French patients with Lynch syndrome. J Med Genet 2020; 57 (07) 487-499
    CrossrefPubMedGoogle Scholar
  • 19 van der Klift HM, Mensenkamp AR, Drost M. et al. Comprehensive mutation analysis of PMS2 in a large cohort of probands suspected of Lynch syndrome or constitutional mismatch repair deficiency syndrome. Hum Mutat 2016; 37 (11) 1162-1179
    CrossrefPubMedGoogle Scholar
  • 20 Goodenberger ML, Thomas BC, Riegert-Johnson D. et al. PMS2 monoallelic mutation carriers: the known unknown. Genet Med 2016; 18 (01) 13-19
    CrossrefPubMedGoogle Scholar
  • 21 Hampel H, Frankel WL, Martin E. et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 2005; 352 (18) 1851-1860
    CrossrefPubMedGoogle Scholar
  • 22 Nakagawa H, Lockman JC, Frankel WL. et al. Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Cancer Res 2004; 64 (14) 4721-4727
    CrossrefPubMedGoogle Scholar
  • 23 Dominguez-Valentin M, Sampson JR, Seppälä TT. et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the prospective Lynch syndrome database. Genet Med 2020; 22 (01) 15-25
    CrossrefPubMedGoogle Scholar
  • 24 Liu YL, Cadoo KA, Maio A. et al. Early age of onset and broad cancer spectrum persist in MSH6- and PMS2-associated Lynch syndrome. Genet Med 2022; 24 (06) 1187-1195
    CrossrefPubMedGoogle Scholar
  • 25 Guo X, Wu W, Gao H. et al. PMS2 germline mutation c.943C>T (p.Arg315*)-induced Lynch syndrome-associated ovarian cancer. Mol Genet Genomic Med 2019; 7 (06) e721
    CrossrefPubMedGoogle Scholar
  • 26 Sheehan M, Heald B, Yanda C. et al. Investigating the link between Lynch syndrome and breast cancer. Eur J Breast Health 2020; 16 (02) 106-109
    CrossrefPubMedGoogle Scholar