Dataset Information

Diverse 'just-right' levels of chromosomal instability and their clinical implications in neoadjuvant treated gastric cancer.

ABSTRACT:

Background

The Cancer Genome Atlas (TCGA) consortium described EBV positivity(+), high microsatellite instability (MSI-H), genomic stability (GS) and chromosomal instability (CIN) as molecular subtypes in gastric carcinomas (GC). We investigated the predictive and prognostic value of these subtypes with emphasis on CIN in the context of neoadjuvant chemotherapy (CTx) in GC.

Methods

TCGA subgroups were determined for 612 resected adenocarcinomas of the stomach and gastro-oesophageal junction (291 without, 321 with CTx) and 143 biopsies before CTx. EBV and MSI-H were analysed by standard assays. CIN was detected by multiplex PCRs analysing 22 microsatellite markers. Besides the TCGA classification, CIN was divided into four CIN-subgroups: low, moderate, substantial, high. Mutation profiling was performed for 52 tumours by next-generation sequencing.

Results

EBV(+) (HR, 0.48; 95% CI, 0.23-1.02), MSI-H (HR, 0.56; 95% CI, 0.35-0.89) and GS (HR, 0.72; 95% CI, 0.45-1.13) were associated with increased survival compared to CIN in the resected tumours. Considering the extended CIN-classification, CIN-substantial was a negative prognostic factor in uni- and multivariable analysis in resected tumours with CTx (each p < 0.05). In biopsies before CTx, CIN-high predicted tumour regression (p = 0.026), but was not prognostically relevant.

Conclusion

A refined CIN classification reveals tumours with different biological characteristics and potential clinical implications.

SUBMITTER: Kohlruss M

PROVIDER: S-EPMC8651679 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Diverse 'just-right' levels of chromosomal instability and their clinical implications in neoadjuvant treated gastric cancer.

Kohlruss Meike M Krenauer Marie M Grosser Bianca B Pfarr Nicole N Jesinghaus Moritz M Slotta-Huspenina Julia J Novotny Alexander A Hapfelmeier Alexander A Schmidt Thomas T Steiger Katja K Gaida Matthias M MM Reiche Magdalena M Bauer Lukas L Ott Katja K Weichert Wilko W Keller Gisela G

British journal of cancer 20211020 12

<h4>Background</h4>The Cancer Genome Atlas (TCGA) consortium described EBV positivity(+), high microsatellite instability (MSI-H), genomic stability (GS) and chromosomal instability (CIN) as molecular subtypes in gastric carcinomas (GC). We investigated the predictive and prognostic value of these subtypes with emphasis on CIN in the context of neoadjuvant chemotherapy (CTx) in GC.<h4>Methods</h4>TCGA subgroups were determined for 612 resected adenocarcinomas of the stomach and gastro-oesophagea ...[more]

PMID: 34671125

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Dataset Information

Diverse 'just-right' levels of chromosomal instability and their clinical implications in neoadjuvant treated gastric cancer.

Background

Methods

Results

Conclusion

Publications

Diverse 'just-right' levels of chromosomal instability and their clinical implications in neoadjuvant treated gastric cancer.

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