Original Article
Comparative Genomic Hybridization Reveals Differences in DNA Copy Number Changes between Sporadic Gastric Carcinomas and Gastric Carcinomas from Patients with Hereditary Nonpolyposis Colorectal Cancer

https://doi.org/10.1016/S0165-4608(98)00046-6Get rights and content

Abstract

Comparative genomic hybridization was used to search for DNA copy number changes in samples of gastric cancer from 12 hereditary nonpolyposis colon cancer (HNPCC) patients and in samples of sporadic gastric carcinoma from 13 patients. The gastric cancer samples from HNPCC patients showed gains affecting 19q, Xp, and whole chromosome 22, each in a single patient. Neither high-level amplifications nor losses of DNA copy number were detected. On the other hand, 10 of the 13 (77%) sporadic gastric carcinoma samples had multiple DNA copy number changes. The most frequent gains occurred with minimal common overlapping regions at 1q22–q31, 8q23–qter, 17p11.2–q22, and 20q, all at a frequency of 31%. High-level amplifications were also seen at 17q21 in three cases (23%). Losses were rare, and the most frequent loss was with a minimal common overlapping region at 4q32 (23%). This suggests that multiple DNA copy number changes are needed for the development of sporadic gastric carcinoma but not for gastric carcinoma in HNPCC patients.

Introduction

Colorectal cancer is the second most common malignancy after smoking-related cancers in Western society [1]. Epidemiological studies have suggested that as many as 15% of colorectal cancers occur in a dominantly inherited pattern 2, 3, 4, 5. The best-defined two familial forms are the polyposis syndrome, accounting for 0.5–1.0% of the patients, and the hereditary nonpolyposis colorectal cancer (HNPCC), affecting 0.5–0.9% of the total colorectal cancer burden 6, 7, 8.

So far, several conventional cytogenetic analyses have failed to describe any specific chromosomal aberration for colorectal cancers 9, 10. Recently, however, comparative genomic hybridization (CGH) analysis performed on both intestinal and diffuse sporadic gastric carcinomas allowed us to demonstrate an amplicon at 17q12–q21 in 36% of the intestinal gastric carcinomas and recurrent gains of DNA sequences at 20q and 8q in both intestinal and diffuse subtypes [11].

To compare the pattern of DNA copy number changes in sporadic gastric carcinoma and gastric carcinoma from HNPCC patients, we performed CGH analysis on both types.

Section snippets

Patients

Twelve paraffin-embedded archival gastric cancer samples were obtained from patients with the Finnish HNPCC. Ten samples originated from families fulfilling the Amsterdam criteria for HNPCC [12]. Nine of these families were shown to segregate an MLH1 mutation. One family did not fulfill the Amsterdam criteria but segregated an MLH1 mutation [13]. Tumors 6 and 10 were derived from families without a known germ-line defect. Tumors, 1, 3, 7, 8, 9, 10, and 11 have been shown to display a

Results and discussion

The present study is the first report of CGH performed on gastric carcinomas derived from HNPCC patients. Three of the 12 HNPCC samples (tumors 1–12) showed gains of DNA sequence copy numbers affecting 19q (tumor 1), chromosome 22 (tumor 5), and Xp (tumor 9). Neither high-level amplifications nor losses of DNA copy number were observed in the samples (Table 1).

However, within the 13 sporadic gastric carcinomas, 10 (77%) had changes with a mean value of 5.1 ± 1.5 aberrations per sample (range, 1

Acknowledgements

We thank Drs. Lauri Aaltonen and Heikki Järvinen for helpful comments and providing HNPCC tumor material. This study was supported by the Helsinki University Central Hospital and the Sigrid Jusélius Foundation in Finland and by the National Council of Scientific and Technological Research (CONICET) and the National University of La Plata in Argentina.

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