Universität zu Köln

Kohlruss, Meike, Krenauer, Marie, Grosser, Bianca, Pfarr, Nicole ORCID: 0000-0002-5977-5375, Jesinghaus, Moritz ORCID: 0000-0002-0018-5661, Slotta-Huspenina, Julia, Novotny, Alexander, Hapfelmeier, Alexander, Schmidt, Thomas, Steiger, Katja ORCID: 0000-0002-7269-5433, Gaida, Matthias M., Reiche, Magdalena, Bauer, Lukas, Ott, Katja, Weichert, Wilko and Keller, Gisela (2021). Diverse 'just-right' levels of chromosomal instability and their clinical implications in neoadjuvant treated gastric cancer. Br. J. Cancer, 125 (12). S. 1621 - 1632. LONDON: SPRINGERNATURE. ISSN 1532-1827

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kohlruss, Meike UNSPECIFIED UNSPECIFIED UNSPECIFIED Krenauer, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Grosser, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfarr, Nicole UNSPECIFIED orcid.org/0000-0002-5977-5375 UNSPECIFIED Jesinghaus, Moritz UNSPECIFIED orcid.org/0000-0002-0018-5661 UNSPECIFIED Slotta-Huspenina, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Novotny, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Hapfelmeier, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Steiger, Katja UNSPECIFIED orcid.org/0000-0002-7269-5433 UNSPECIFIED Gaida, Matthias M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiche, Magdalena UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Ott, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Weichert, Wilko UNSPECIFIED UNSPECIFIED UNSPECIFIED Keller, Gisela UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-596734
DOI:	10.1038/s41416-021-01587-4
Journal or Publication Title:	Br. J. Cancer
Volume:	125
Number:	12
Page Range:	S. 1621 - 1632
Date:	2021
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1532-1827
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPSTEIN-BARR-VIRUS; MICROSATELLITE INSTABILITY; MOLECULAR ANALYSIS; MICROENVIRONMENT; ADENOCARCINOMAS; CHEMOTHERAPY; PROFILES Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59673