Cytogenetic differences between intestinal and diffuse types of human gastric carcinoma

Saal, Kim‐Ann; Hp, Vollmers; Müller, Justus; Köhler, Julia R.; Höhn, H; Hk, Müller-Hermelink

doi:10.1007/bf02915107

Cited by 16 publications

(9 citation statements)

References 24 publications

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“…The most consistently observed imbalances were gains, in the order of their frequency, of chromosome arms 20q, 16p, 11q, 1q, and 7q. Only the most frequent imbalance, gain of chromosome 20 (70%), had been described before as a recurrent genetic change in this tumor type (Saal et al, 1993;Seruca et al, 1993). CGH analysis allowed us to narrow down the critical region further to the commonly gained segment 20q12-q13.1 defined by tumor 19 (see Fig.…”

Section: Discussionmentioning

confidence: 98%

Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN , MET , WNT2 , and ERBB2

Neßling

Solinas‐Toldo

Wilgenbus

et al. 1998

Genes Chromosomes & Cancer

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Gastric adenocarcinoma is a malignant tumor with a high incidence and a low survival rate. In order to identify genetic alterations associated with this tumor, we screened 23 gastric adenocarcinomas for recurrent chromosomal imbalances by using comparative genomic hybridization (CGH). The most common gains of chromosomal material were found on chromosome arms 20q (10 cases), 16p (7 cases), and 1q (4 cases) and on chromosome 11 (4 cases). Losses were observed on chromosome arms 4q, 5q, 9p, and 21q (3 cases each). Four tumors exhibited high‐level amplifications localized on chromosome regions 2p23–p24, 7q31–q32, 8p21–p22, 10q25–q26, 11q13, 17q11–q21, and 20q. Based on the position of these amplifications, candidate (onco)genes were selected and subsequently tested by Southern blot analysis of the respective tumors. Of the seven tested candidates, MYCN, MET, WNT2, and ERBB2 were found to participate in the amplicons of the respective tumor samples. Of these four presumably activated oncogenes, two, MYCN and WNT2, were previously not assumed to play a pathogenic role in stomach cancer. Among the other regions of imbalance, gain of 20q seems particularly interesting, because it is found in almost half of the analyzed cases and is highly amplified. Our data allowed us to narrow the relevant region down to the commonly gained bands 20q12–q13.1. This and other imbalanced regions provide a basis for searching new putative oncogenes and tumor suppressor genes involved in the development or progression of gastric adenocarcinoma. Genes Chromosomes Cancer 23:307–316, 1998. © 1998 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 98%

Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN , MET , WNT2 , and ERBB2

Neßling

Solinas‐Toldo

Wilgenbus

et al. 1998

Genes Chromosomes & Cancer

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“…Almost all GINs also have high degree CK7 positivity. Molecular studies indicate fewer critical steps for the tumorigenesis of diffuse types than intestinal types of carcinoma [38,59], and intermediate steps of GIN are assumed to occur in the development of the intestinal, but usually not in the diffuse types [59]. Recent findings indicate that intestinalization of signet ring cell carcinomas occurs, but usually as a time-dependent switch starting primarily with a gastric phenotype [3].…”

Section: Discussionmentioning

confidence: 99%

Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis

et al. 2001

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Cancer presumably arises from stem cells, preserved in an undifferentiated status since fetal development, or from a dedifferentiation of mature cells that return into a fetal phenotype with the potential for proliferation and renewal. Dedifferentiation in this context could represent a transient phase, passed through by cells, before they switch to redifferentiation, metaplasia or neoplasia. Cytokeratin-7 (CK7) is present in fetal, largely absent in normal adult, and transiently neoexpressed in metaplastic and neoplastic epithelial cells of the stomach according to previous observations. CK7 neoexpression in the stomach could, hence, define a fetal-like, dedifferentiated, cellular phenotype during the development of metaplasia and neoplasia. To test this hypothesis, we investigated CK7 expressions in fetal stomachs, non-neoplastic control stomachs, and neoplastic stomachs exhibiting metaplasia, intraepithelial neoplasia, and early cancer. Proliferation and beta-catenin expression of CK7-positive cells were also evaluated. The chronology of CK7 expression was studied during the experimental gastritis-cancer sequence in Mongolian gerbils. Our results show that metaplastic and neoplastic changes in the gastritis-cancer sequence are related to dedifferentiated epithelial cells which are defined by CK7 expression and can phenotypically be linked to fetal cells at the start of gastric pit development. The dedifferentiated cells exhibit a low proliferation and beta-catenin accumulation, similar to stem cells. Thus, the "stem cell" and "dedifferentiation" hypotheses for cancer origin could complement one another, and dedifferentiation-redifferentiation processes might be decisive for carcinogenesis in the stomach.

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“…Trisomy 20 has been detected frequently in intestinal-type GC by karyotyping analyses. 22) El-Rifai et al 14) reported the 20q gain to be a consistent aberration in intestinal-type adenocarcinoma of the gastro-esophageal region. Although the biological significance is not clear, 20q gain of GC is more common in the lower third stomach than in the middle third stomach (P=0.002).…”

Section: Discussionmentioning

confidence: 99%

DNA Sequence Copy Number Aberrations Associated with Histological Subtypes and DNA Ploidy in Gastric Carcinoma

Oga

Park

Kawauchi

et al. 2001

Japanese Journal of Cancer Research

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We have analyzed DNA sequence copy number aberrations (DSCNAs) and DNA ploidy by using comparative genomic hybridization and laser scanning cytometer in gastric carcinomas (GCs) to elucidate the genomic aberrations in relation to clinicopathological parameters. Thirty-two out of 33 cases showed one or more DSCNAs with a mean number of 11.7 per tumor. High-level gains were detected at 2p, 3q, 6p, 7p, 7q, 8q, 12p, 13q, 19q, and 20q. Frequency of gross genomic abnormalities and chromosome regions that have genomic aberrations were similar in both intestinaland diffuse-type GCs, except aberrations at 8p, 9p, 12q, and 20q. The overall number of DSCNAs was significantly greater in DNA aneuploid tumors than that in DNA diploid tumors. We detected genomic aberrations characterized by histological subtype, tumor location, and DNA ploidy status: gain of 20q and losses of 8p and 9p in intestinal-type GCs, gains of 8p and 12q in diffuse-type GCs, gain of 20q in the lower third GCs, and loss of 5q, 9p, 10q, 16q, and 18q in DNA aneuploid GCs. Furthermore, 5q loss is associated with DNA aneuploidy (P = = = =0.0001) or the total number of losses (P = = = =0.001), gain + + + +losses (P = = = =0.004), and high-level gains (P = = = =0.001) in GCs. Among these loci, chromosome 8p was unique. Gain of 8p was more common in diffuse-type GC, whereas loss of 8p was more frequently detected in intestinal-type GC. In conclusion, we describe chromosomal regions of 5q, 8p, and 20q, which are of interest for further investigation of GCs.

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Cytogenetic differences between intestinal and diffuse types of human gastric carcinoma

Cited by 16 publications

References 24 publications

Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN , MET , WNT2 , and ERBB2

Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN , MET , WNT2 , and ERBB2

Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis

DNA Sequence Copy Number Aberrations Associated with Histological Subtypes and DNA Ploidy in Gastric Carcinoma

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