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Integrated genomic characterization of endometrial carcinoma
  • D. Levine, Gad Stacey B. Kristian Eric Andrey Carrie Mike Cyriac Getz Gabriel Cibulskis Lander Sivachenko Sougnez L, +271 authors H. Sofia
  • Biology, Medicine
  • 1 May 2013
The genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours, and these features are classified into four categories: POLE ultramutated, microsatellite instability hypermutated, copy- number low, and copy-number high.
Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC.
Evidence is presented that sequence changes within the coding region of the RET proto-oncogene, a putative transmembrane tyrosine kinase, may be responsible for the development of neoplasia in these inherited disorders.
Genome Remodeling in a Basal-like Breast Cancer Metastasis and Xenograft
The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within thePrimary tumour.
DICER1 Mutations in Familial Pleuropulmonary Blastoma
It is hypothesize that loss of DICER1 in the epithelium of the developing lung alters the regulation of diffusible factors that promote mesenchymal proliferation.
The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia
It is demonstrated that TBX22 is a major gene determinant crucial to human palatogenesis, and the spectrum of nonsense, splice-site, frameshift and missense mutations the authors have identified indicates that the cleft phenotype results from a complete loss ofTBX22 function.
Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers
Investigating MSI and MLH1 promoter methylation in 441 endometrial cancer patients unselected for age or personal and family history of cancers suggested that inherited defects in MSH6 in women with endometricrial cancer are relatively common, comparable with the predicted prevalence for patients with colorectal cancer.
MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers.
Observations suggest that epigenetic changes in the MLH1 locus account for MSI in most cases of sporadic endometrial cancers and provide additional evidence that the MSH2 gene may contribute substantially to inherited forms ofendometrial cancer.
Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B.
It is proposed that a point mutation in the RET protooncogene results in the replacement of methionine with threonine within the catalytic core region of the tyrosine kinase domain, which results in dominant oncogenic activity by the RET protein.
Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes
The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrioid carcinoma.
Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer.
This work presents a new paradigm in which hypermethylation-mediated silencing of a microRNA derepresses its oncogenic target in cancer cells, and finds a significant correlation of hypermethylated miR-129-2 with microsatellite instability and MLH1 methylation status and poor overall survival in patients.