An investigation of the Peutz-Jeghers gene (LKB1) in sporadic breast and colon cancers

Abstract

Aims-To explore the role of the PeutzJeghers gene (LKB1) in sporadic breast and colon cancers. Methods-Thirty consecutive sporadic carcinomas of the breast and 23 of the colon were selected. DNA was extracted from paraYn wax embedded tissue and analysed for loss of heterozygosity (LOH) at microsatellite markers D19S886 and D19S565 close to the LKB1 gene. Tumours showing LOH were screened for LKB1 mutations by single strand conformational polymorphism (SSCP). Results-Five breast carcinomas showed LOH (21% and 7% of those informative for D19S886 and D19S565, respectively). Five of the colorectal carcinomas showed LOH (15% and 36% of those informative for D19S886 and D19S565, respectively), with one sample showing allele loss with both markers. Screening of these 10 carcinomas by SSCP identified one migrational shift but sequencing revealed an intronic polymorphism only. Therefore, no coding mutations were found in these carcinomas. Conclusions-These findings suggest that although allele loss at the LKB1 locus occurs relatively frequently in sporadic breast and colon cancers, mutations do not seem to be a feature. (J Clin Pathol 2000;53:791-793)

LKB1; linking cell structure and tumor suppression

“…Mutational analysis across a range of sporadic tumors has identified loss of function LKB1 mutations most frequently in non-small cell lung carcinomas; between 5 and 17% of cases depending on the population studied (Sanchez-Cespedes et al, 2002;Ji et al, 2007;Koivunen et al, 2008). Somatic inactivating mutations in LKB1 have also been reported in approximately 5% of pancreatic cancers and melanomas, and in single specimens of prostate cancer and cervical cancer (Avizienyte et al, , 1999Bignell et al, 1998;Wang et al, 1998;Guldberg et al, 1999;Rowan et al, 1999;Su et al, 1999;Forster et al, 2000;Ikediobi et al, 2006). Overall, the incidence of LKB1 mutation in sporadic cancers, other than lung cancer, appears low despite the high penetrance of carcinomas associated with PJS.…”

Germline Mutation of the LKB1/STK11 Gene with Loss of the Normal Allele in an Aggressive Breast Cancer of Peutz-Jeghers Syndrome

“…Shen et al [17]reported that LKB1/STK11 plays a role in the tumor suppressor function in sporadic breast cancer, and low expression of the LKB1/STK11 protein is significantly associated with a shorter survival. However, several attempts have failed to show the somatic mutation of LKB1/STK11 in breast cancer [18, 19, 20]. …”

Suppression of oncogenic properties of c-Myc by LKB1-controlled epithelial organization

“…Recent findings have also shown evidence that human LKB1 (PAR4) and its target AMPactivated protein kinase control polarity and assembly of tight junction structures in mammalian epithelial cells (13)(14)(15). LKB1 is also defined as a human tumor suppressor protein because germline Lkb1-inactivating mutations characterize Peutz-Jeghers cancer syndrome families, and, furthermore, somatic alterations or reduced gene expression of LKB1 are found in several carcinomas, including carcinomas of breast (16)(17)(18)(19)(20).…”