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

J 2020

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

SNAHNICANOVA, Zuzana, Ivana KASUBOVA, Michal KALMAN, Marian GRENDAR, Peter MIKOLAJCIK et. al.

Basic information

Original name

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

Authors

SNAHNICANOVA, Zuzana (703 Slovakia), Ivana KASUBOVA (703 Slovakia), Michal KALMAN (703 Slovakia), Marian GRENDAR (703 Slovakia), Peter MIKOLAJCIK (703 Slovakia), Eva GABONOVA (703 Slovakia), Ludovit LACA (703 Slovakia), Martin CAPRNDA (703 Slovakia), Luis RODRIGO (724 Spain), Rachele CICCOCIOPPO (380 Italy), Peter KRUŽLIAK (703 Slovakia, guarantor, belonging to the institution), Lukas PLANK (703 Slovakia) and Zora LASABOVA (703 Slovakia)

Edition

Clinical and Experimental Medicine, Milan, SPRINGER-VERLAG ITALIA SRL, 2020, 1591-8890

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30109 Pathology

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.984

RIV identification code

RIV/00216224:14110/20:00115437

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1007/s10238-019-00601-7

UT WoS

000511988900011

Keywords in English

Colorectal cancer; Cancer immunogenicity; Microsatellite instability; Beta-2-microglobulin; Promoter methylation

Abstract

V originále

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.

Citovat

SNAHNICANOVA, Zuzana, Ivana KASUBOVA, Michal KALMAN, Marian GRENDAR, Peter MIKOLAJCIK, Eva GABONOVA, Ludovit LACA, Martin CAPRNDA, Luis RODRIGO, Rachele CICCOCIOPPO, Peter KRUŽLIAK, Lukas PLANK and Zora LASABOVA. Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer. Clinical and Experimental Medicine. Milan: SPRINGER-VERLAG ITALIA SRL, 2020, vol. 20, No 1, p. 87-95. ISSN 1591-8890. Available from: https://dx.doi.org/10.1007/s10238-019-00601-7.

@article{1637736,
   author = {Snahnicanova, Zuzana and Kasubova, Ivana and Kalman, Michal and Grendar, Marian and Mikolajcik, Peter and Gabonova, Eva and Laca, Ludovit and Caprnda, Martin and Rodrigo, Luis and Ciccocioppo, Rachele and Kružliak, Peter and Plank, Lukas and Lasabova, Zora},
   article_location = {Milan},
   article_number = {1},
   doi = {http://dx.doi.org/10.1007/s10238-019-00601-7},
   keywords = {Colorectal cancer; Cancer immunogenicity; Microsatellite instability; Beta-2-microglobulin; Promoter methylation},
   language = {eng},
   issn = {1591-8890},
   journal = {Clinical and Experimental Medicine},
   title = {Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer},
   url = {http://dx.doi.org/10.1007/s10238-019-00601-7},
   volume = {20},
   year = {2020}
}

TY  - JOUR
ID  - 1637736
AU  - Snahnicanova, Zuzana - Kasubova, Ivana - Kalman, Michal - Grendar, Marian - Mikolajcik, Peter - Gabonova, Eva - Laca, Ludovit - Caprnda, Martin - Rodrigo, Luis - Ciccocioppo, Rachele - Kružliak, Peter - Plank, Lukas - Lasabova, Zora
PY  - 2020
TI  - Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer
JF  - Clinical and Experimental Medicine
VL  - 20
IS  - 1
SP  - 87-95
EP  - 87-95
PB  - SPRINGER-VERLAG ITALIA SRL
SN  - 15918890
KW  - Colorectal cancer
KW  - Cancer immunogenicity
KW  - Microsatellite instability
KW  - Beta-2-microglobulin
KW  - Promoter methylation
UR  - http://dx.doi.org/10.1007/s10238-019-00601-7
L2  - http://dx.doi.org/10.1007/s10238-019-00601-7
N2  - 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.
ER  -

SNAHNICANOVA, Zuzana, Ivana KASUBOVA, Michal KALMAN, Marian GRENDAR, Peter MIKOLAJCIK, Eva GABONOVA, Ludovit LACA, Martin CAPRNDA, Luis RODRIGO, Rachele CICCOCIOPPO, Peter KRUŽLIAK, Lukas PLANK and Zora LASABOVA. Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer. \textit{Clinical and Experimental Medicine}. Milan: SPRINGER-VERLAG ITALIA SRL, 2020, vol.~20, No~1, p.~87-95. ISSN~1591-8890. Available from: https://dx.doi.org/10.1007/s10238-019-00601-7.

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