Abstract 5716
Background
Mutations in genes involved into antigen presentation such as B2M are enriched among colorectal cancer (CRC) patients with high microsatellite instability (MSI-H) and can become negative predictors for checkpoint inhibitor therapy. The aim of this study was the determination of prevalence of B2M somatic mutations in MSI-H CRC patients and relationship between B2M mutations and lymphocytes infiltration and other clinicopathological features. We focused also for methylation status of B2M promoter as another possible mechanism of gene expression downregulation.
Methods
From our study group enrolling 420 CRC patients, 37 MSI-H and 5 MSI-L patients were selected for screening of B2M mutational status. The characterization of patients was based on standard histopathological diagnosis, TNM classification, tumor-infiltrating lymphocytes and peritumoral lymphoid reactions were determined. MSI analysis was performed using fragment analysis. BRAF, KRAS and B2M mutational status were identified by Sanger sequencing. For methylation analysis of B2M promoter region was used nested methylation specific PCR.
Results
B2M mutations were detected in 5 MSI-H patients (13.5%). In four cases, heterozygous mutation c.45_48delTTCT located in exon 1 was present and 2 patients exhibited heterozygous mutation c.276delC in exon 2. From group of 5 MSI-H patients, one case was compound heterozygote for both these mutations. Methylation of B2M promoter was observed only in 1 MSI-H case from our study group.
Conclusions
The presence of B2M mutations should be correlated with the response to the checkpoint inhibitor therapy in order to improve patient’s stratification and also development of new immunotherapeutic approaches. Our pilot study recommends detection of CpG methylation in B2M gene for the future studies in the area of colorectal cancer.
Clinical trial identification
Editorial acknowledgement
Biomedical Center Martin (ITMS 26220220187), APVV-16-0066 and VEGA 1/0380/18.
Legal entity responsible for the study
The authors.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3353 - Results of the 3rd interim analysis of C-Patrol: A non-interventional study on olaparib in German routine clinical practice
Presenter: Jalid Sehouli
Session: Poster Display session 2
Resources:
Abstract
740 - A real-world analysis of the treatment of advanced ovarian cancer with PARPIs
Presenter: Alejandra Martinez de Pinillos
Session: Poster Display session 2
Resources:
Abstract
5867 - Incidence of tumour BRCA1/2 variants in relapsed, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer
Presenter: Robert Morgan
Session: Poster Display session 2
Resources:
Abstract
2966 - Frequency of mutations in 21 hereditary breast and ovarian cancer susceptibility genes among 882 high-risk individuals
Presenter: Jihong Liu
Session: Poster Display session 2
Resources:
Abstract
1687 - BRCA testing of 1,284 Brazilian patients for hereditary breast and ovarian cancer in a routine diagnostic setting
Presenter: Fernanda Milanezi
Session: Poster Display session 2
Resources:
Abstract
3162 - A multi-center integrative study on cancer predisposition genes in Chinese patients with epithelial ovarian carcinoma
Presenter: Changbin Zhu
Session: Poster Display session 2
Resources:
Abstract
5993 - Incidental Early Occult Ovarian Cancer after Risk-Reducing Salpingo-Oophorectomy in BRCA1/2 Mutation Carriers followed in a Community Public Hospital
Presenter: Begona Grana Suarez
Session: Poster Display session 2
Resources:
Abstract
5334 - Response to chemotherapy in ovarian cancer (OC) patients with or without prior breast cancer (BC), stratified by BRCA mutation (BRCAm) status
Presenter: Angela George
Session: Poster Display session 2
Resources:
Abstract
4565 - Advanced ovarian cancer: is residual disease after debulking surgery affected by genetics factors involved in angiogenesis and immunity pathways?
Presenter: Michele Bartoletti
Session: Poster Display session 2
Resources:
Abstract
3251 - Surrogate endpoint of progression-free (PFS) and overall survival (OS) for advanced ovarian cancer (AOC) patients (pts) treated with neo-adjuvant chemotherapy (NACT): Results of the CHIVA randomized phase II GINECO study
Presenter: Fabrice Lecuru
Session: Poster Display session 2
Resources:
Abstract