In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16674-e16674
Abstract:
e16674 Background: Next-generation sequencing (NGS) has been used to identify actionable mutations in biliary tract cancers (BTCs). IDH1 is an enzyme that catalyzes the conversion of isocitrate to alpha-ketoglutarate, and is involved in the tricarboxylic acid cycle. Mutations in IDH1 are associated with aberrant conversion of alpha- ketoglutarate to 2-hydroxyglutarate, which is an oncogenic metabolite. In addition, IDH1 showed an effective biomarker for cholangiocarcinoma targeted therapy in the ClarIDHy study. Therefore, the detection of IDH1 mutations is essential for predicting sensitivity to targeted therapy. Methods: Deep sequencing targeting 450 cancer genes was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matching blood samples that collected from a cohort of 926 Chinese BTC patients, including 469 intrahepatic (ICC), 203 extrahepatic (ECC), 195 gallbladder cancers (GC), and 59 hilar (HCCA) cholangiocarcinoma. Single nucleotide variations (SNV), short and long insertions/deletions (Indels), copy number variations, gene rearrangements, and fusions, were analyzed. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: IDH1 mutations were detected in 3.9% patients, with a median age of 59 years old. The rate of IDH1 mutations was 7% in ICC, 1% in ECC, 0.5% in GC, and 0% in HCCA. IDH1 R132C (75.8%) substitution was the most common type of IDH1 mutation in ICC. In BTC patients, ARID1A (25%), TP53 (22%), and PBRM1 (22%) were the top-ranked co-mutation genes with IDH1. Compared with the IDH1 wild-type cohort, the frequencies of KRAS and TP53 mutations were significantly lower in the IDH1 mutated cohort (29.3% vs. 2.8%, p = 0.001; 56.6% vs. 22.2%, p 〈 0.001). In addition, IDH1 mutations were associated with a significantly lower TMB value compared to the wild-type cases (average TMB: 3.2 vs. 5.8 muts/Mb, p 〈 0.001). Conclusions: To date, this was the largest cohort used to study the characterization of IDH1 mutations in Chinese BTCs. The mutation frequency of IDH1 was lower in Chinese ICCs compared with non-Asian populations (7.0% vs. 16.5%). Consistent with the results from previous reports, IDH1 R132C substitution was the most common type of IDH1 mutation in ICCs (PMID: 31392056). TMB value and the frequency of TP53 and KRAS mutations were lower in patients with IDH1 mutation, which may provide clues for sensitivity to targeted therapy and prognosis.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e16674
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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