Molecular-genetic profiling of patients with adenomatous polyps of the gastrointestinal tract

   Aim: to reveal hereditary mutations in patients with adenomatous polyps of the gastrointestinal tract.
   Patients and methods: a retrospective cohort study included 8 patients with adenomatous polyps of the gastrointestinal tract (ranging from 4 to several hundred). The APC, AXIN2, BMPR1A, BRCA2, CDH1, CHEK2, EPCAM, GALNT12, GREM1, MLH1, MLH3, MSH2, MSH3, MSH6, MutYH, NTHL1, PMS2, POLD1, POLE, SMAD4, STK11 genes were studied using new generation sequencing.
   Results: five patients were found to have pathogenic mutations in the genes APC (3 patients with > 100 polyps), POLE (1 patient with < 10 polyps), MutYH (1 patient with 2 mutations with > 28 polyps; 1 patient with monoallelic mutation in combination with a mutation in the APC gene with a number of polyps > 100).

   Conclusion: the probability of detecting a pathogenic mutation increases with an increase in the number of polyps in a patient.

1. Huang Y., Gong W., Su B., et al. Recurrence and surveillance of colorectal adenoma after polypectomy in a southern Chinese population. J Gastroenterol. 2010; 45: 838–45. DOI: 10.1007/s00535-010-0227-3

2. Hao Y., Wang Y., Qi M., et al. Risk Factors for Recurrent Colorectal Polyps. Gut Liver. 2020; 14: 399–411. DOI: 10.5009/gnl19097

3. Colorectal cancer screening. Practical guide of the World Gastroenterological Society (WGO) and the International Union for the Prevention of Cancer of the Digestive System. WGO. 2008. (in Russ.).

4. Brosens L. A. A., Wood L. D., Offerhaus G. J., et al. Pathology and Genetics of Syndromic Gastric Polyps. Int J Surg Pathol. 2016; 24: 185–99. DOI: 10.1177/1066896915620013

5. Half E., Bercovich D., Rozen P. Familial adenomatous polyposis. Orphanet J Rare Dis. 2009; 4: 22. DOI: 10.1186/1750-1172-4-22

6. Powell S. M., Zilz N., Beazer-Barclay Y., et al. APC mutations occur early during colorectal tumorigenesis. Nature. 1992; 359: 235–7. DOI: 10.1038/359235a0

7. Tsukanov A. S., Shubin V. P., Kuzminov A. M. et al. Differential diagnosis of MutYH-associated polyposis and sporadic colon polyps. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018; 28 (6): 51–57. (In Russ.). DOI: 10.22416/1382-4376-2018-28-6-51-57

8. Knudsen A. L., Bisgaard M. L., Bülow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam Cancer. 2003; 2: 43–55. DOI: 10.1023/a:1023286520725

9. Tsukanov A. S. Strategy of complex molecular genetic study of hereditary forms of colorectal cancer in Russian patients (abstract. … doctor of medical sciences). Moscow. 2017; 48 р. (In Russ.).

10. Toboeva M. K., Shelygin Yu. A., Frolov S. A., et al. MutYH-associated polyposis. Ter Arkh. 2019;91(2):97–100. (in Russ.). DOI: 10.26442/00403660.2019.02.000124

11. Nielsen M., Infante E., Brand R. MutYH Polyposis. In: Adam M. P., Ardinger H. H., Pagon R. A., et al. GeneReviews®. Seattle (WA): University of Washington, Seattle 1993. http://www.ncbi.nlm.nih.gov/books/NBK107219/ (accessed 25 Jan 2022).

12. Testa U., Pelosi E., Castelli G. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells. Med Sci (Basel). 2018; 6: E31. DOI: 10.3390/medsci6020031

13. Weren R. D., Ligtenberg M. J., Geurts van Kessel A., et al. NTHL1 and MutYH polyposis syndromes: two sides of the same coin? J Pathol. 2018; 244: 135–42. DOI: 10.1002/path.5002

14. Adam R., Spier I., Zhao B., et al. Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis. Am J Hum Genet. 2016; 99: 337–51. DOI: 10.1016/j.ajhg.2016.06.015

15. Abramov I. S., Lisitsa T. S., Stroganova A. M., et al. Diagnostics of hereditary cancer syndromes by ngs. A database creation experience. Journal of Clinical Practice. 2021;12(3):36–42. (in Russ.). DOI: 10.17816/clinpract76383

16. Richards S., Aziz N., Bale S., et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17: 405–24. DOI: 10.1038/gim.2015.30

17. 17 Bellido F., Pineda M., Aiza G., et al. POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. Genet Med. 2016;18(4):325–32. DOI: 10.1038/gim.2015.75