Abstract
Chromosomal instability (CIN) is a hallmark of distinct subclasses of tumours with potential clinical relevance. The aim of our study was to establish a time and cost effective method for the determination of CIN in gastric carcinomas (GC). We developed a microsatellite based multiplex PCR assay for the detection of allelic imbalances (AI) using experimentally defined marker specific threshold values for AI. The assay was tested in 90 formalin-fixed paraffin-embedded GC and results were compared in a subset of 30 carcinomas with the Affymetrix OncoScan assay, which detects copy number variations on genome wide level. The ratios of alterations detected by the two methods demonstrated a significant correlation (r = 0.88). Based on the results of the OncoScan assay, tumours were classified in CIN-High and CIN-Low and a threshold of the AI ratio determined with the PCR assay was defined. Accordingly, 20 of the 90 GC (22%) were CIN-Low and 70 (78%) CIN-High. A significant association of CIN-High was found with intestinal type tumours and proximal tumour localization. In conclusion, we established a PCR based method to categorize AI as surrogate for CIN, which is easy to perform and useful for the clarification of the clinical relevance of CIN in large GC cohorts.
Highlights
The development of genomic instability is considered to endow cells with genetic alterations that drive cancer development and progression
Chromosomal instability (CIN) in the TCGA study of gastric carcinomas (GC) and of oesophageal adenocarcinomas refers to the description of the extent of chromosomal alterations in the tumours mainly determined by genome-wide single nucleotide polymorphism (SNP) based microarray technology[3,6,7]
Performance of the assay was tested on a cohort of GC and the results were compared to those from the Affymetrix OncoScan assay in a subset of the tumours to define a classification of CIN based on both methods
Summary
The development of genomic instability is considered to endow cells with genetic alterations that drive cancer development and progression. Chromosomal instability (CIN) is considered to be a main driving force for the frequently observed aneuploidy of tumour cells. CIN in the TCGA study of GC and of oesophageal adenocarcinomas refers to the description of the extent of chromosomal alterations in the tumours mainly determined by genome-wide single nucleotide polymorphism (SNP) based microarray technology[3,6,7]. This approach, is obviously not suited for routine diagnostics www.nature.com/scientificreports/. The aim of our study was to establish a relatively simple and cost effective method for the determination of CIN in GC, which should be applicable to DNA isolated from formalin-fixed paraffin-embedded (FFPE) tumour tissues
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