Somatic mutations in the STK11/LKB1 gene are uncommon in rare gynecological tumor types associated with Peutz-Jegher's syndrome

Peutz-Jegher's syndrome (PJS) is a rare autosomal dominant disorder charact erized by mucocutaneous pigmentation, hamartomatous polyposis, and predispo sition to benign and malignant tumors of the gastrointestinal tract, breast , ovary, uterine cervix, and testis. Germline-inactivating mutations in one allele of the STX11/LKB1 gene at chromosome 19p13.3 have been found in mos t PJS patients. Although ovarian sex cord tumors with annular tubules (SCTA Ts) and minimal deviation adenocarcinomas (MDAs) of the uterine cervix are very rare in the general population, both tumor types occur with increased frequency in women with PJS, An earlier report indicated that the 19p13.3 r egion containing the STK11 gene was affected by loss of heterozygosity (LOB ) in nearly 50% of MDAs of the uterine cervix, We investigated the role of STX11 mutations and LOH of the 19p13.3 region in two PJS-associated SCTATs and in five SCTATs and eight MDAs of the uterine cervix, which occurred in patients lacking features of PJS (referred to here as "sporadic" cases). Ge rmline mutations in the STX11 gene, accompanied by LOH of markers near the wildtype STK11 allele, were found in the two PJS-associated SCTATs, Somatic mutations in the coding region of STX11 were not found in any of the spora dic SCTATs or MDAs studied, although LOH of the 19p13.3 region was seen in three of eight MDAs, Our findings indicate that S21K11, like other tumor su ppressor genes, is affected by biallelic inactivation in gynecological tumo rs of PJS patients. in addition, although LOH of the 19p13.3 region was see n in sporadic MDAs, somatic STK11 mutations are rare. A yet-to-be-defined t umor suppressor gene in the 19p13.3 region may be the specific target of in activation in these tumors.