✦ LIBER ✦

Low frequency of BRAF and CDKN2A mutations in endometrial cancer

✍ Scribed by Helga B. Salvesen; Rajiv Kumar; Ingunn Stefansson; Sabrina Angelini; Nicola MacDonald; Johanna Smeds; Ian J. Jacobs; Kari Hemminki; Soma Das; Lars A. Akslen

Publisher: John Wiley and Sons
Year: 2005
Tongue: French
Weight: 196 KB
Volume: 115
Category: Article
ISSN: 0020-7136
DOI: 10.1002/ijc.20702

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Several pathways have been implicated in the pathogenesis of endometrial carcinoma. Based on recent reports, BRAF mutations provide an alternative route for activation of the RAS signalling pathway. The CDKN2A (p16) tumour suppressor gene is also altered in several tumour types. We therefore wanted to assess the pattern and prognostic impact of BRAF mutations and p16 alterations in endometrial carcinomas. Only 1 of 48 tumours (2%) was found to have a BRAF mutation in exon 15, whereas 8 of 45 tumours (18%) had a K‐ras mutation. Homozygous deletion, amplification, promoter region methylation or mutation of the p16 gene was seen in 6 cases (13%), and 18 cases (38%) carried polymorphisms in the p16 gene. All tumours with presence of p16 methylation, non‐sense mutation, deletion or amplification exhibited loss of p16 expression as evaluated by immunohistochemistry. Presence of a p16 hit was significantly correlated with high FIGO stage (p = 0.04), high histologic grade (p = 0.02), estrogen receptor negativity (p = 0.05), pathologic expression of p53 (p = 0.02), pathologic expression of p16 (p = 0.05) and poor survival (p = 0.02). There was also a significant correlation between loss of p16 expression and K‐ras mutations, pathologic p53 expression and serous papillary/clear cell histologic types (p = 0.05/p = 0.001/p = 0.002). In conclusion, BRAF mutation is an infrequent finding in endometrial carcinomas. Loss of p16 expression is seen in all cases with alterations of the p16 gene. The presence of a p16 hit might be important in a subset of endometrial carcinomas with aggressive clinical behaviour. However, the mechanism of p16 inactivation remains unclear for the majority of cases exhibiting loss of expression, but the interactions with K‐ras and p53 should be further studied. © 2005 Wiley‐Liss, Inc.

📜 SIMILAR VOLUMES

Low frequency of CDKN2 mutation in endom

Low frequency of CDKN2 mutation in endometrial carcinomas

✍ Stacia L. Peiffer; Detlef Bartsch; Alison J. Whelan; David G. Mutch; Thomas J. H 📂 Article 📅 1995 🏛 John Wiley and Sons 🌐 English ⚖ 309 KB

## Abstract The __CDKN2__ gene on chromosome 9p21 encodes the p16 inhibitor of cyclin D/cyclin‐dependent kinase 4 complexes. Mutations and deletions of __CDKN2__ have been frequently identified in cell lines, whereas most primary tumors have demonstrated a lower frequency of alteration. To assess t

Frequency of KRAS, BRAF, and NRAS mutati

Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer

✍ Cecily P. Vaughn; Scott D. ZoBell; Larissa V. Furtado; Christine L. Baker; Wade 📂 Article 📅 2011 🏛 John Wiley and Sons 🌐 English ⚖ 85 KB 👁 1 views

## Abstract Mutational analysis of __KRAS__ codons 12 and 13 is standard for patients with metastatic colorectal cancer since mutations in these codons predict lack of response to anti‐EGFR therapies. However, even among patients whose tumors are wildtype for __KRAS__ codons 12 and 13, only a subse

Low frequency of p16/CDKN2 gene mutation

Low frequency of p16/CDKN2 gene mutations in esophageal carcinomas

✍ Asunción Esteve; Ghyslaine Martel-Planche; Bakary S. Sylla; Monica Hollstein; Pi 📂 Article 📅 1996 🏛 John Wiley and Sons 🌐 French ⚖ 515 KB

Mutational analysis of the pl6ICDKN2 gene was conducted by direct sequencing of the whole coding sequence (exom 1-3 and flanking splicing sites) in 21 esophageal squamous-cell carcinomas and 3 adenocarcinomas from a high-incidence area of Italy. Two inactivating mutations were found in exon I of the

Retention of the CDKN2A locus and low fr

Retention of the CDKN2A locus and low frequency of point mutations in primary and metastasic cutaneous malignant melanoma

✍ Anna Ruiz; Susana Puig; Michael Lynch; Teresa Castel; Xavier Estivill 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 French ⚖ 124 KB 👁 2 views

CDKN2A has been found mutated in melanoma families which show linkage to chromosome 9p21. In contrast, a low mutation rate has been found in melanomas, suggesting that CDKN2A might not be the first target for mutation in the development of this type of tumour. To elucidate the role of the CDKN2A gen

Low frequency of AXIN2 mutations and hig

Low frequency of AXIN2 mutations and high frequency of MUTYH mutations in patients with multiple polyposis

✍ Sophie Lejeune; François Guillemot; Jean-Pierre Triboulet; Stéphane Cattan; Chri 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 English ⚖ 106 KB

## Communicated by Riccardo Fodde Familial adenomatous polyposis has been linked to germline mutations in the APC tumor suppressor gene. However, a number of patients with familial adenomatous polyposis (with either classical or attenuated phenotype) have no APC mutation. Recently, germline mutatio

Predicting functional significance of ca

Predicting functional significance of cancer-associated p16INK4a mutations in CDKN2A

✍ Heather A. McKenzie; Carina Fung; Therese M. Becker; Mal Irvine; Graham J. Mann; 📂 Article 📅 2010 🏛 John Wiley and Sons 🌐 English ⚖ 350 KB 👁 1 views

Inherited mutations affecting the INK4a/ARF locus (CDKN2A) are associated with melanoma susceptibility in 40% of multiple case melanoma families. Over 60 different germline INK4a/ARF mutations have been detected in more than 190 families worldwide. The majority of these alterations are missense muta