当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Altered messenger RNA and unique mutational profiles of p53 and Rb in human esophageal carcinomas.

Altered messenger RNA and unique mutational profiles of p53 and Rb in human esophageal carcinomas.

Abstract：

:Seventy-nine esophageal carcinoma patients were studied for genetic abnormalities in the p53 and Rb tumor suppressor genes. Single-strand conformation polymorphism analysis and DNA sequencing were used to detect p53 point mutations, Northern blotting was used to examine abnormal expression of p53 and Rb, and polymerase chain reaction and Southern blotting were used to analyze allelic loss. Twenty-five cases were analyzed by DNA sequencing to detect mutations in p53. Fourteen samples contained mutations within exons 5 through 9 of p53; seven had missense mutations giving rise to single amino acid substitutions. The remaining seven (50%) contained nonsense mutations leading to premature termination, five due to single base pair substitutions, and two that were the result of frameshift mutations. In other human tumors, p53 mutations are predominantly missense mutations, but our data as well as those from other groups show that nonsense mutations are common in human esophageal cancer. All but one of the constitutionally heterozygous samples containing mutations also manifested loss of the normal p53 allele; the one exception without allelic loss contained a silent mutation, which should not have had any affect on the p53 protein product. In addition, Northern blotting analysis revealed abnormalities (altered transcript size or mRNA levels) in 5 of 7 cases involving p53 and in 2 of 7 cases analyzed for Rb. Thirty-four cases were informative for allelic loss studies of both p53 and Rb; of these, 25 (74%) lost heterozygosity of p53, Rb, or both. When point mutations and mRNA expression abnormalities were also considered, 33 of 45 (73%) tumors informative for allelic loss assays of both genes as well as for mRNA or point mutation studies showed one or more abnormalities in p53 or Rb. Our results strongly suggest that a unique profile of molecular alterations involving p53 and Rb characterizes human esophageal cancer and that these specific genetic lesions are important in the development and/or progression of most human esophageal carcinomas.

journal_name

Cancer Res

journal_title

Cancer research

authors

Huang Y,Meltzer SJ,Yin J,Tong Y,Chang EH,Srivastava S,McDaniel T,Boynton RF,Zou ZQ

subject

Has Abstract

pub_date

1993-04-15 00:00:00

pages

1889-94

issue

eissn

0008-5472

issn

1538-7445

journal_volume

pub_type

杂志文章

在线工具

Altered messenger RNA and unique mutational profiles of p53 and Rb in human esophageal carcinomas.