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Erschienen in: Clinical and Experimental Medicine 1/2020

01.02.2020 | Original Article

Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer

verfasst von: Zuzana Snahnicanova, Ivana Kasubova, Michal Kalman, Marian Grendar, Peter Mikolajcik, Eva Gabonova, Ludovit Laca, Martin Caprnda, Luis Rodrigo, Rachele Ciccocioppo, Peter Kruzliak, Lukas Plank, Zora Lasabova

Erschienen in: Clinical and Experimental Medicine | Ausgabe 1/2020

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Abstract

One of the most common mechanisms of immune evasion in MSI colorectal cancers (CRCs) is loss of HLA class I expression due to mutations in B2M gene which can become a negative predictor for checkpoint blockade therapy. The aim of this study was the determination of prevalence of B2M somatic mutations in MSI CRC patients and relationship between B2M mutations and lymphocytes infiltration and other clinicopathological features as well as detection of methylation changes in B2M promoter region which can be another mechanism of immune escape. In our study, 37 MSI-H and 5 MSI-L patients were selected for screening of B2M mutational and methylation status. The characterization of patients was based on standard histopathological diagnosis and TNM classification; BRAF, KRAS mutations, tumor-infiltrating lymphocytes and peritumoral lymphoid reaction were also determined. MSI analysis was performed using fragment analysis. B2M mutations were identified by Sanger sequencing, and methylation of CpG islands in promoter region was detected by methylation-specific PCR. Heterozygous mutations in the B2M gene were detected in five MSI-H patients (13.5%), while the mutation c.45_48delTTCT was determined in four patients and mutation c.276delC was found in two patients. One of these five patients was compound heterozygote harboring both mutations. Methylation of the promoter region of the B2M gene was observed in one patient with MSI-H colorectal cancer. Detection of genetic and epigenetic changes in B2M gene could be important in personalized therapy for CRC patients as these changes may be one of the mechanisms of secondary resistance of MSI positive tumors to immunotherapy.
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Metadaten
Titel
Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer
verfasst von
Zuzana Snahnicanova
Ivana Kasubova
Michal Kalman
Marian Grendar
Peter Mikolajcik
Eva Gabonova
Ludovit Laca
Martin Caprnda
Luis Rodrigo
Rachele Ciccocioppo
Peter Kruzliak
Lukas Plank
Zora Lasabova
Publikationsdatum
01.02.2020
Verlag
Springer International Publishing
Erschienen in
Clinical and Experimental Medicine / Ausgabe 1/2020
Print ISSN: 1591-8890
Elektronische ISSN: 1591-9528
DOI
https://doi.org/10.1007/s10238-019-00601-7

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