TY - JOUR
T1 - A microsatellite based multiplex PCR method for the detection of chromosomal instability in gastric cancer
AU - Kohlruss, Meike
AU - Reiche, Magdalena
AU - Jesinghaus, Moritz
AU - Grosser, Bianca
AU - Slotta-Huspenina, Julia
AU - Hapfelmeier, Alexander
AU - Bauer, Lukas
AU - Novotny, Alexander
AU - Weichert, Wilko
AU - Keller, Gisela
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85052522669&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-30971-z
DO - 10.1038/s41598-018-30971-z
M3 - Article
C2 - 30135548
AN - SCOPUS:85052522669
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12551
ER -