In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e16066-e16066
Abstract:
e16066 Background: Gastric cancer (GCA) is one of the most deadly cancers all over the world, with an estimate of 26,560 new cases and 11,180 deaths in United States according to the cancer statistics of 2021. As immunotherapy has become available for GCA, it is necessary to distinguish patients who might be resistant to it. Methods: We identified 41 patients with amplified MET from a large Chinese cohort including 934 GCA (4.4% out of them) according to the ratio of purity adjusted copy number of MET and chromosome 7. Then, we comprehensively profiled genomic characteristics related to immunotherapy for GCA with amplified MET and compared them with other GCA. Results: First, mutated RNF43 and AXIN1 were much more prevalent in GCA with amplified MET. These two genes are components of Wnt pathway, whose aberrance is associated with resistance to immunotherapy. Second, carrier ratios of amplified CDK6 and CCND1 were much higher in GCA with amplified MET. These two genes play important roles in cell cycle pathway, while amplification of CCND1 has been recognized as a negatively predictive biomarker for immunotherapy. Third, we calculated mutational load of immunotherapy-related positively (mutated ATM, BRCA1, BRCA2, CHEK2, ERCC2, ERCC4, FANCA, KRAS, MLH1, MSH2, MSH6, NRAS, PALB2, PBRM1, PMS2, POLD1, POLE, RAD50 and TP53; deleted POLE) and negatively (mutated B2M, CTNNB1, DNMT3A, EGFR, JAK1, JAK2 and STK11; amplified CCND1, EGFR, FGF19, FGF3, FGF4, MDM2 and MDM4; deleted B2M, JAK2, PTEN and STK11) predictive biomarkers for GCA with amplified MET. We defined the mutational load as mean carrier ratio of point mutations or copy number variations (CNVs) appeared in a gene set. As is expected, the mutational load of point mutations in 19 positively predictive biomarkers in GCA with amplified MET was much lower than that in other GCA, whereas the mutational load of CNV in 11 negatively predictive biomarkers in GCA with amplified MET was much higher than that in other GCA. Finally, we found GCA with amplified MET possessed lower tumor mutational burden (TMB) and microsatellite instability (MSI), depleted somatic signature of defective DNA mismatch repair and higher copy number instability (CNI). Conclusions: Genomic characteristics of GCA with amplified MET are associated with adverse response to immunotherapy and thus it should be carefully evaluated when these patients are treated with immunotherapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2021.39.15_suppl.e16066
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2021
detail.hit.zdb_id:
2005181-5
