Rapidly and Slowly Growing Lineages in Chromosomal Instability-Type Gland-Forming Gastric Carcinomas as Revealed by Multisampling Analysis of DNA Copy-Number Profile

Autor:	Takahisa Nakayama, Ken-ichi Mukaisho, Hiroyuki Sugihara, Tu Thanh Duong, Masamichi Bamba, Diem Thi-Ngoc Vo, Trung Sao Nguyen
Rok vydání:	2019
Předmět:	Male DNA Copy Number Variations Locus (genetics) In situ hybridization Adenocarcinoma Biology Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Chromosome instability medicine Humans Cell Lineage Molecular Biology Lymph node Aged Oligonucleotide Array Sequence Analysis Aged 80 and over Comparative Genomic Hybridization Paraffin Embedding Genome Human Array-based comparative genomic hybridization Stomach Cell Biology General Medicine Middle Aged medicine.disease Molecular biology Chromosomal instability genomic DNA medicine.anatomical_structure Gastric Mucosa Tissue Array Analysis 030220 oncology & carcinogenesis Female DNA mismatch repair Copy-number alterations Metastasis risk 030215 immunology Comparative genomic hybridization
Zdroj:	Pathobiology. 86:118-127
ISSN:	1423-0291 1015-2008
DOI:	10.1159/000494926
Popis:	BACKGROUND:To examine whether gastric carcinoma (GC) with chromosomal instability (CIN-type GC), the largest category in the Cancer Genome Atlas classification, consists of a single genetic lineage, we conducted a multisampling analysis of genomic DNA copy-number profile. METHODS:We performed array-based comparative genomic hybridization using formalin-fixed paraffin-embedded tissues from 54 gland-forming GCs containing a total of 106 DNA samples from mucosal, extramucosal invasive, and lymph node lesions. Microarray data were analyzed by unsupervised hierarchical clustering and penetrance plots. Epstein-Barr virus infection status and mismatch repair(MMR) enzyme-silencing/p53/mucin expression were examined by in situ hybridization and immunohistochemistry, respectively. RESULTS:The samples examined were divided into gain-rich cluster A and loss-rich cluster B, which were different in tumor locus and patient age. The T1/T2-4 ratio, the frequency of small cancers (diameter 2-4 cm), and intestinal mucin expression were higher in cluster B than in cluster A, but there were no significant differences in the frequencies of MMR silencing, mutant p53 pattern, and lymph node metastasis between the 2 clusters. CONCLUSIONS:We demonstrated that CIN-type GC could be categorized into 2 genetic lineages which are different in terms of rapidity of local extension but similar in terms of nodal metastasis risk.
Databáze:	OpenAIRE
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