Mixed Gastric Carcinomas Show Similar Chromosomal Aberrations in Both their Diffuse and Glandular Components

Beatriz Carvalho,Tineke E Buffart,Thomas Mons,Gerrit A Meijer,Cátia Moutinho,Bauke Ylstra,Nicole C T Van Grieken,Paula Silva,Rui M Reis,Fátima Carneiro,Cornelis J H Van De Velde,Heike Grabsch

doi:10.1155/2006/650620

Abstract

Gastric cancer is one of the most frequent malignancies in the world. Nonetheless, the knowledge of the molecular events involved in the development of gastric carcinoma is far from complete. One of the hallmarks of gastric cancer is chromosomal instability resulting in abnormal DNA copy number changes throughout the genome. Mixed gastric carcinomas constitute a rare histological entity, containing the two main histological phenotypes (diffuse and intestinal). Very little is known about the underlying mechanisms of phenotypic divergence in these mixed tumours. To the best of our knowledge only E-Cadherin mutations were implicated so far in the divergence of these tumours and nothing is known about the involvement of chromosome copy number changes in the two divergent histological components. In this study, we compared the DNA copy number changes, in the two different components (diffuse and intestinal) of mixed gastric carcinomas by microarray – comparative genomic hybridisation (array CGH). The analysis of 12 mixed gastric carcinomas showed no significant differences in array CGH profiles between the diffuse and intestinal components of mixed carcinomas. This supports the idea that the phenotypic divergence within mixed gastric carcinomas is not caused by DNA chromosomal aberrations.

Highlights

Despite the overall decrease in incidence and mortality rates, gastric cancer remains the second most frequent malignancy worldwide [25,26]
The amplification observed on 8q spans a region of 3.9 Mb and contains 7 genes (TRMT12, RNF139, TATDN1, MTSS1, TRIB1, FAM84B and c-MYC)
We hypothesised that DNA copy changes might underlie the phenotypic divergence observed in mixed gastric carcinomas

Summary

Introduction

Despite the overall decrease in incidence and mortality rates, gastric cancer remains the second most frequent malignancy worldwide [25,26]. Two main histological types of gastric cancer are recognized, the intestinal [22] or glandular carcinoma [5] and the diffuse [22] or isolated-cell type carcinoma [5]. Distinct genetic pathways underlie these two types of gastric cancer. Mutations in particular genes are restricted to one of the two histological types, such as mutations in CDH1 (the gene encoding for the adhesion molecule E-cadherin) that occur only in diffuse gastric carcinoma [1,10] or amplification, and over-expression, of the ERBB2

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Results

Conclusion