STK11 Domain XI Mutations: Candidate Genetic Drivers Leading to the Development of Dysplastic Polyps in Peutz – Jeghers Syndrome
发表时间：2014-07-12 14:44
ABSTRACT
Peutz–Jeghers syndrome (PJS) is a rare hereditary disorder resulting from mutations in ser- ine/threonine kinase 11 (STK11) and characterized by gastrointestinal (GI) hamartomatous polyps, mucocuta- neous pigmentation, and an increased risk for specific cancers. Little is known about the genetic implications of specific STK11 mutations with regard to their role in dysplastic and malignant transformation of GI polyps. Pe- ripheral blood genomic DNA samples from 116 Chinese PJS patients from 52 unrelated families were investigated for STK11 mutations. Genotype–phenotype correlations were investigated. The mutation detection rate was 67.3% (51.9% point mutations, 15.4% large deletions). Four- teen out of the 25 point mutations identified were novel. Nearly one-third of all mutations, 8/27 (29.6%), were in exon 7, the shortest out of the nine exons. Strikingly, mutations affecting protein kinase domain XI, encoded in part by exon 7, correlated with a 90% (9/10) inci- dence of GI polyp dysplasia. In contrast, only two out of 17 (11.8%) nondomain XI mutations were linked to polyp dysplasia (P = 0.0001). The extent of the associa- tion between dysplasia and the development of GI-related cancers is currently unknown but our results highlight a novel STK11 genotype–phenotype association as the basis for future genetic counseling and basic research studies. Hum Mutat 35:851–858, 2014. C ? 2014 Wiley Periodicals, Inc.
KEY WORDS
dysplastic polyp; hereditary cancer; malignancy; Peutz–Jeghers syndrome; STK11; LKB1
第一署名医院：南方医科大学南方医院
