Abstract 123P
Background
BLM (BLM RecQ Like Helicase) is a DNA helicase that plays an important role in maintaining genomic integrity. Researches have shown that dysfunction of BLM was associated with PD-L1 expression. This study aimed to reveal the relation between BLM-mutant and BLM-wild type tumors in tumor mutation burden (TMB) and microsatellite instability (MSI).
Methods
We retrospectively analyzed the BLM mutations of 15189 Chinese patients with pan-cancer during 2019-2021(Simcere Diagnosis, Nanjing, China). Next-generation sequencing (NGS) assessed somatic mutations in tumor tissue. We figured out BLM mutation frequency, TMB and MSI in BLM-mutant, BLM wild-type.
Results
BLM mutants were detected in 267 (1.8%) samples. The top 5 frequent cancers were lung cancer (66, 24.7%), colorectal cancer (64, 24.0%), liver cancer (31, 11.0%), gastric cancer (20, 7.5%) and endometrial cancer (12, 4.2%). BLM variants included missense/indel/insert (80.2%),truncation (10.5%), CNV (7.1%) splicing site variant (1.9%), and fusion (0.3%). The inactive variants are either frameshift mutations or splicing mutations, recurring in a few hot spots (N515Mfs*16/fs/Kfs*2, D757Tfs*4). And we found that the TMB and MSI in the BLM mutation group was significantly higher than that in the BLM wild-type group[TMB-H (TMB ≥10 musts/Mb): BLM-MUT vs BLM-WT, 52.1% vs 9.1%, p < 0.01; MSI-H: BLM-MUT vs BLM-WT, 27.0% vs1.0% p < 0.01]. And then, we separately analyzed the correlation between MSI, TMB and BLM gene mutation in the top 5 frequent cancers. Over 80% of patients with BLM mutations in colorectal and endometrial cancers have high TMB values[colorectal cancer (BLM-MUT vs BLM-WT, 87.5% vs 8.4%, p<0.001); endometrial cancer (BLM-MUT vs BLM-WT, 81.8% vs 17.4%, p<0.01)].
Conclusions
We analyzed BLM gene mutations in Chinese patients with solid tumor. Our data showed that BLM mutations were associated with higher TMB and MSI in solid tumors. Especially in colorectal cancer and endometrial cancer, over 80% of patients with BLM mutations have high TMB values. In short, our data showed that BLM mutations are important molecular marker of immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.