Patterns of CDKN2A gene loss in sequential oral epithelial dysplasias and carcinomas.

نویسندگان

  • S A Shahnavaz
  • G Bradley
  • J A Regezi
  • N Thakker
  • L Gao
  • D Hogg
  • R C Jordan
چکیده

The CDKN2A gene locus encodes two different proteins derived from alternative splicing. p16 (exons 1alpha, 2, and 3) acts as a G1 cell cycle regulator, and p14ARF (exons 1beta, 2, and 3) acts to modulate MDM2-mediated degradation of p53. Inactivation of p16 is a common finding in many cancers; however, there is little data on CDKN2A gene abnormalities in oral precancer. In this longitudinal study, we examined changes in the CDKN2A gene locus in sequential epithelial dysplasias and oral carcinomas from 11 patients. Genomic DNA was extracted from laser-microdissected lesional tissue, and exons 1alpha, 1beta, and 2 were analyzed by duplex PCR. Immunohistochemistry was done to identify p16 and p14ARF protein expression. Two adjacent polymorphic microsatellite markers were used for allelotyping. Homozygous deletion of exon 1alpha was identified in 2 of 17 (12%) precancerous lesions. Loss of either exon 1alpha, exon 2, or both was seen in seven of nine (78%) carcinomas. In five of these carcinomas, there was loss of only exon 1alpha. No case showed deletion of exon 1beta. In 5 of 11 patients, microsatellite markers showed differing patterns of allelic imbalance in the precancerous lesions and the subsequent carcinoma, suggesting a complex genetic pattern of progression from dysplasia to carcinoma. We conclude that during oral carcinogenesis homozygous deletion of exon 1alpha of the CDKN2A gene is common but that deletion of exon 2 and 1beta is less frequent. Moreover, our results suggest that the progression from oral precancer to cancer, in some cases, is more complex genetically than predicted by linear models of carcinogenesis.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

E-cadherin, laminin and collagen IV expression in the evolution from dysplasia to oral squamous cell carcinoma.

OBJECTIVES Study the loss or reduction of the cellular adhesion mediated for E-cadherin in oral leukoplakias, oral squamous cell carcinomas and metastatic nodules. Study the loss of continuity of the laminin and collagen IV expression in the epithelial basal membrane from the biological development of the oral leukoplakias and oral carcinomas. MATERIAL AND METHOD we have studied 124 samples o...

متن کامل

Frequent Alterations of p16 and p14 in Oral Proliferative Verrucous Leukoplakia

Proliferative verrucous leukoplakia (PVL) represents a rare but highly aggressive form of oral leukoplakia with >70% progressing to malignancy. Yet, PVL remains biologically and genetically poorly understood. This study evaluated the cell cycle regulatory genes, p16 and p14 , for homozygous deletion, loss of heterozygosity, and mutation events in 20 PVL cases. Deletion of exon 1B, 1A, or 2 was ...

متن کامل

متیلاسیون اگزون 1، ژن CDKN2A در نمونه‌های بلوک پارافینه سرطان روده بزرگ

Background: The molecular studies indicate some of the genes in the promoter region itself, will undergo methylation. Methylation of CpG islands in the promoter region of that cause silence or reduced expression of genes involved in cell growth pathways, which are colorectal cancer causing agents. Detection of methylation status can be used as a marker for cancer diagnosis and prediction of dis...

متن کامل

Epigenetic Inactivation of 14-3-3 in Oral Carcinoma: Association with p16 Silencing and Human Papillomavirus Negativity

In vitro studies have identified 14-3-3 as a regulator of senescence in human keratinocytes. To assess its contribution to squamous neoplasia, we have analyzed genetic and epigenetic changes in this gene in squamous cell carcinomas (SCCs) and dysplastic lesions of the oral cavity. No mutations were detected in the coding sequence of 14-3-3 in 20 oral carcinomas, and there was loss of heterozygo...

متن کامل

Increased expression of CENP-H gene in human oral squamous cell carcinomas harboring high-proliferative activity.

We examined the expression of Centromere protein H (CENP-H) mRNA in 38 oral squamous cell carcinomas (SCCs), 2 epithelial dysplasias and 5 normal gingivae using the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean expression level of CENP-H mRNA was higher in oral SCCs (0.11+/-0.08) than epithelial dysplasias (0.03+/-0.01) and normal gingivae (0.027+/-0....

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cancer research

دوره 61 6  شماره 

صفحات  -

تاریخ انتشار 2001