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.

Základní údaje

Originální název

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

Autoři

SNAHNICANOVA, Zuzana (703 Slovensko), Ivana KASUBOVA (703 Slovensko), Michal KALMAN (703 Slovensko), Marian GRENDAR (703 Slovensko), Peter MIKOLAJCIK (703 Slovensko), Eva GABONOVA (703 Slovensko), Ludovit LACA (703 Slovensko), Martin CAPRNDA (703 Slovensko), Luis RODRIGO (724 Španělsko), Rachele CICCOCIOPPO (380 Itálie), Peter KRUŽLIAK (703 Slovensko, garant, domácí), Lukas PLANK (703 Slovensko) a Zora LASABOVA (703 Slovensko)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30109 Pathology

Stát vydavatele

Itálie

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.984

Kód RIV

RIV/00216224:14110/20:00115437

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000511988900011

Klíčová slova anglicky

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

Štítky

14110121, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 20. 3. 2020 12:18, Mgr. Tereza Miškechová

Anotace

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 a 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, roč. 20, č. 1, s. 87-95. ISSN 1591-8890. Dostupné z: 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 a 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, roč.~20, č.~1, s.~87-95. ISSN~1591-8890. Dostupné z: https://dx.doi.org/10.1007/s10238-019-00601-7.

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