Dataset Information

Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

ABSTRACT:

Background

The goal of this study is to disclose the clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

Methods

A total of 86 Chinese patients were enrolled in this study. A panel of 579 pan-cancer genes was sequenced for the qualified samples from these patients. Driver genes, actionability, and tumor mutational burden were inferred and compared to a cohort of Western patients.

Results

Totally, 36 and 12 driver genes were identified in the Chinese and Western cohorts, respectively. Of them, seven driver genes (IDH1, KRAS, TP53, BAP1, PBRM1, ARID1A, and NRAS) were shared by the two cohorts. Four driver genes (SPTA1, ARID2, TP53, and GATA1) were found significantly correlated with the tumor mutational burden. For both cohorts, half of the patients had actionable mutations. The two cohorts shared the most actionable genes but differed much in their frequency. Though KRAS mutations were at the first and second actionable rank respectively for the Chinese and Western populations, they were still at a relatively low level of actionable evidence.

Conclusions

The study on the clinical significance of genomic alterations directs the future development of precision medicine for intrahepatic cholangiocarcinoma treatment.

SUBMITTER: Xu S

PROVIDER: S-EPMC7879680 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

Xu Shifeng S Guo Yuan Y Zeng Yanwu Y Song Zhijian Z Zhu Xiaodan X Fan Ning N Zhang Zhilei Z Ren Guibing G Zang Yunjin Y Rao Wei W

BMC cancer 20210212 1

<h4>Background</h4>The goal of this study is to disclose the clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.<h4>Methods</h4>A total of 86 Chinese patients were enrolled in this study. A panel of 579 pan-cancer genes was sequenced for the qualified samples from these patients. Driver genes, actionability, and tumor mutational burden were inferred and compared to a cohort of Western patients.<h4>Results</h4>Totally, 36 and 12 dri ...[more]

PMID: 33579226

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Project description:Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer arising from the bile ducts with a need for earlier diagnosis and a greater range of treatment options. KRAS/NRAS mutations are common in ICC tumours and 6-32% of patients also have isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) gene mutations associated with metabolic changes. This feasibility study investigated sequencing circulating tumour DNA (ctDNA) combined with metabolite profiling of plasma as a method for biomarker discovery in ICC patients. Plasma was collected from four ICC patients receiving radio-embolisation and healthy controls at multiple time points. ctDNA was sequenced using Ampliseq cancer hotspot panel-v2 on Ion Torrent PGM for single nucleotide variants (SNV) detection and with Illumina whole genome sequencing for copy number variants (CNV) and further targeted examination for SNVs. Untargeted analysis of metabolites from patient and control plasma was performed using liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS). Metabolite identification was performed using multi-parameter comparisons with analysis of authentic standards, and univariate statistical analysis was performed to identify differences in metabolite abundance between patient and control samples. Recurrent somatic SNVs and CNVs were identified in ctDNA from three out of four patients that included both NRAS and IDH1 mutations linked to ICC. Plasma metabolite analysis revealed biomarker metabolites associated with ICC and in particular 2-hydroxyglutarate (2-HG) levels were elevated in both samples from the only patient showing a variant allele in IDH1. A reduction in the number of CNVs was observed with treatment. This study demonstrates that ctDNA and metabolite levels can be identified and correlated in ICC patient blood samples and differentiated from healthy controls. We conclude that combining genomic and metabolic analysis of plasma offers an effective approach to biomarker identification with potential for disease stratification and early detection studies.

Dataset Information

Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

Background

Methods

Results

Conclusions

Publications

Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

Similar Datasets

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