Abstract 57P
Background
The isocitrate dehydrogenase (IDH) is an important enzyme in the tricarboxylic acid cycle and IDH mutations play an important role in tumor treatment and prognosis evaluation. IDH mutations have been reported in approximately 15% of cholangiocarcinoma (CCA) patients, while these aberrations are considered to be less frequent in other bile duct carcinoma (BDC) patients. IDH inhibitors have been approved for targeted therapy, which holds great promise for improving the management of BDCs. Here we provide an overview of IDH mutations in a large cohort of Chinese BDCs.
Methods
BDC tissue specimens and/or circulating cell-free DNA from patients who had undergone molecular profiling were retrospectively reviewed. IDH1, IDH2 and other BDC related genes were detected using hybridization-based targeted next-generation sequencing.
Results
A total of 874 Chinese BDC cases had undergone molecular profiling from January 2017 to March 2021. We identified 60 IDH mutations in 59 of the 874 patients. Of these patients, Active-site mutations in IDH1 and IDH2 (IDH1_R132, IDH2_R140 and IDH2_R172) were detected in 50 patients (5.72%, 50/874), including 28 (56%) males and 22 (44%) females. The median age of patients with IDH active-site mutations was 57.5 years old (age range 32–79 years). Among the 60 IDH mutations, missense variation was the most frequent mutation category (98.3%, 59/60), and the other one was frameshift. Out of the 36 IDH1 active-site mutated specimens, 27 (75%) carried IDH1 R132C mutations, followed by IDH1-R132L (11.1%), IDH1-R132S (8.3%) and IDH1-R132G (5.6%). 14 patients harbored IDH2 active-site mutations, including IDH2-R172W (78.6%), IDH2-R172K (7.14%), IDH2-R172M (7.14%) and IDH2-R140Q (7.14%). Among the 50 activating IDH mutations patients, co-variations in TP53 (7, 14%), KRAS (7, 14%), ARID1A (7, 14%), KMT2C (3, 6%) and BAP1 (3, 6%) were observed. Compared to other patients, the activating IDH mutations group had a relatively lower TMB (Median 3.97 vs 2.86, p=0.09).
Conclusions
We elucidate the molecular and clinicopathological characteristics of IDH mutant BDCs from a large number of Chinese patients to provide foundational knowledge on personalized clinical management for IDH-directed therapy.
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.