SO35: DNA-diagnostics of Familial Adenomatous Polyposis and Peutz-Jeghers syndrome among Russian patients

N.I. Pospekhova, V.P. Shubin, I.Y. Sachkov, A.M. Kuzminov, V.N. Kashnikov, Y.A. Shelygin, A.S. Tsukanov

State Scientific Center of Coloproctology, Moscow, Russia

Aim

Familial Adenomatous Polyposis (FAP) and Peutz-Jeghers syndrome (PJS) are responsible for 1% of colorectal cancer cases. FAP is caused by germline mutations in APC gene. PJS is caused by germline mutations in STK11 gene. The aim of this investigation was to study the frequency of  APC and STK11 mutations in the Russian patient cohort.

Method

We collected 107 blood samples of  FAP patients and 7 samples of PJS patients. Germline mutations in APC and STK11 genes were analyzed by PCR, electrophoresis, Sanger Sequencing and Next-Generation Sequencing.

Results

Germline mutations in APC were detected in 77 from 107 cases. Six mutations were recurring: p.Arg232X (2 cases), p.Asp849GlufsX11 (2 cases) p.Arg216X (3 cases), p.Gln1062X (5 cases), p.Arg213X (5 cases), p.Glu1309AspfsX4 (16 cases). Forty four mutations were frameshift, 28 – nonsense, and  5 – splice site mutations. Five germline mutations in STK11 were detected among  7 PJS patients. Three mutations were frameshift, 1 – splice sites and 1 pathogenic missense mutations.

Conclusion

The frequency of APC and STK11 mutations in Russian patients with FAP and PJS were 72% and 71% respectively. Twenty two mutations in both genes are described for the first time.

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