Titel (eng)

Serial Analysis of Gene Mutations and Gene Expression during First-Line Chemotherapy against Metastatic Colorectal Cancer: Identification of Potentially Actionable Targets within the Multicenter Prospective Biomarker Study REVEAL

Autor*in

Jörg Kumbrink   Ludwig Maximilian University Munich / German Cancer Consortium

Julian W. Holch   Ludwig Maximilian University Munich / German Cancer Consortium

Volker Heinemann   Ludwig Maximilian University Munich / German Cancer Consortium

Reinhold Schäfer   German Cancer Consortium / Charité-Universitätsmedizin Berlin

Thomas Kirchner   Ludwig Maximilian University Munich / German Cancer Consortium

Andreas Jung   Ludwig Maximilian University Munich / German Cancer Consortium

Sebastian Stintzing   German Cancer Consortium / German Cancer Research Center / Charité-Universitätsmedizin

Arndt Stahler   German Cancer Consortium / Charité-Universitätsmedizin

Dominik Paul Modest   German Cancer Consortium / Charité-Universitätsmedizin

Michael von Bergwelt-Baildon   Ludwig Maximilian University Munich / German Cancer Consortium

Frederick Klauschen   Ludwig Maximilian University Munich / German Cancer Consortium

Jens Neumann   Ludwig Maximilian University Munich / German Cancer Consortium

Harald Bartsch   Ludwig Maximilian University Munich

Marlies Michl   Ludwig Maximilian University Munich

Florian Kaiser   VK&K Studien GbR

Dirk Hempel   Steinbeis Transfer Institute Clinical Hematology-Oncology

Stefan Kasper   University Hospital Essen

Hana Algül   Technical University of Munich

Sylvie Lorenzen    echnical University of Munich

Pan Li   Ludwig Maximilian University Munich

Daniela Peilstöcker   Ludwig Maximilian University Munich

Torben Redmer   University of Veterinary Medicine Vienna

Soulafa Mamlouk   German Cancer Consortium / Charité-Universitätsmedizin Berlin

Lisa Bohlmann   Ludwig Maximilian University Munich

Verlag

MDPI

Beschreibung (eng)

Most metastatic colorectal cancer (mCRC) patients succumb to refractory disease due to secondary chemotherapy resistance. To elucidate the molecular changes associated with secondary resistance, we recruited 64 patients with mCRC and hepatic metastases before standard first-line chemotherapy between 2014 and 2018. We subjected DNA from primary tumor specimens (P), hepatic metastasis specimens after treatment (M), and liquid biopsies (L) taken prior to (pre), during (intra), and after (post) treatment to next generation sequencing. We performed Nanostring expression analysis in P and M specimens. Comparative bioinformatics and statistical analysis revealed typical mutational patterns with frequent alterations in TP53, APC, and KRAS in P specimens (n = 48). P and pre-L (n = 42), as well as matched P and M (n = 30), displayed a similar mutation spectrum. In contrast, gene expression profiles classified P (n = 31) and M (n = 23), distinguishable by up-regulation of immune/cytokine receptor and autophagy programs. Switching of consensus molecular subtypes from P to M occurred in 58.3% of cases. M signature genes SFRP2 and SPP1 associated with inferior survival, as validated in an independent cohort. Molecular changes during first-line treatment were detectable by expression profiling rather than by mutational tumor and liquid biopsy analyses. SFRP2 and SPP1 may serve as biomarkers and/or actionable targets.

Sprache des Objekts

Englisch

Datum

2022

Rechte

Dieses Werk bzw. dieser Inhalt steht unter einer
CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Klassifikation

Folfiri Plus Cetuximab; Ras Mutations; Bevacizumab; Therapy; Osteopontin; Relevance

Mitglied in der/den Collection(s) (1)