Differentiation of Lynch syndrome from other forms of non-polyposis colorectal cancer among Russian patients

Aim of investigation. Lynch's syndrome is hereditary syndrome caused by germline mutation in one of reparation genes not coupled bases and causing high risk of colorectal cancer development. At present there are no criteria, allowing to reveal all mutation carriers, and development of new guidelines is still going on, that became a task for original study. Material and methods. Search of microsatellite instability (MSI), characteristic for Lynch's syndrome, was carried out in tumor samples of 73 patients by fragment analysis method. At its detection search of germline mutations by polymerase chain reaction methods, electrophoresis and direct sequencing was carried out.

Results. Microsatellite instability was found out in 17 neoplastic samples (23%, 17 of 73). At 9 person germline mutations that has allowed to attribute this group to patients to Lynch's syndrome were revealed. Three of 9 mutations were described for the first time in the world.

Conclusions. According to neoplastic MSI, age and family history two new criteria for Lynch's syndrome search in the Russian patients have been offered. Efficacy of the first criterion was 60%, that of the second — 85,7%.

1. Давыдов М. И., Аксель Е. М. Статистика злокачественных нообразований в России и странах СНГ в 2009 г. // Вестн. РОНЦ им. Н. Н. Блохина РАМН.— 2011. — Т. 22, № 3 (85). — Прил. 1.

2. Цуканов А. С., Поспехова Н. И., Любченко Л. Н. и др. Молекулярно-генетический анализ генов наследственной предрасположенности к раку желудка // Мед. генетика.— 2007.— № 12. — С. 30–34.

3. Geiersbach K. B., Samowitz W. S. Microsatellite instability and colorectal cancer // Arch. Pathol. Lab. Med.—2011. — N 135 (10). — Р.1269–77.

4. Lynch H. T., Lynch P. M., Lanspa S. J. et al. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications// Clin. Genet.— 2009. — N 76. — P. 1–18.

5. Peltomaki P. Lynch syndrome genes // Familial Cancer.— 2005. — N 4. — Р. 227–32.

6. Pérez-Cabornero L., Infante M., Velasco E. et al. Genotype–phenotype correlation in MMR mutation-positive families with Lynch syndrome // Int. J. Colorectal Dis.— 2013. — N 28 (9). — Р. 1195–201.

7. Potter J., Lindor N. Genetics of colorectal cancer // Springer.— 2008. — Р. 185.

8. Umar A., Boland C. R. Terdiman J. P. et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability // J. Natl. Cancer Inst.— 2004. — Vol. 96. — P. 261–8.

9. Vasen H., Möslein G., Alonso A. et al. Guidelines for the clinical management of Lynch syndrome (hereditary nonpolyposis cancer) // J. Med. Genet.— 2007. — N 44. — Р. 353–62.

10. Vasen H. F., Blanco I., Aktan-Collan K. et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts // Gut.— 2013. — N 62. — Р. 812–23.

11. Vasen H. F., Mecklin J. P., Khan P. M. et al. International Collaborative Group on hereditary non-polyposis colorectal cancer (ICG-HNPCC) // Dis. Colon Rectum.— 1991. — Vol. 34. — P. 424–5.

12. Vasen H. F., Moslein G., Alonso A. et al. Recommendations to improve identification of hereditary and familial colorectal cancer in Europe // Fam. Cancer.—2010. — N 9. — Р. 109–15.

13. Vasen H. F., Watsan P., Mecklin J. P. et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC // Gastroenterology.—1999. — Vol. 116. — P. 1453–6.

14. Wagner A., Barrows A., Wijnen J. T. et al. Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: High mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene // Am. J. Hum. Genet.— 2003. — N 72. — Р. 1088–100.

15. Weissman S. M., Burt R., Church J. et al. Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National society of genetic counselors and the collaborative group of the Americas on inherited colorectal cancer joint practice guideline // J. Genet. Couns.— 2012. — N 21 (4). — Р. 484–93.