Guoping Jiang1, Wu Zhang1, Ting Wang1, Songming Ding1, Xiaoliang Shi2, Shuirong Zhang2, Weiwei Shi2, Angen Liu2, Shusen Zheng3. 1. The Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, Zhejiang, P.R. China. 2. OrigiMed Co. Ltd, Shanghai, P.R. China. 3. The Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Abstract
OBJECTIVE: Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Here, we aimed to identify the genomic profile of CCA and provided molecular evidence for further biomarker development. METHODS: The formalin-fixed paraffin-embedded and matching blood samples were sequenced by deep sequencing targeting 450 cancer genes and genomic alteration analysis was performed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most commonly altered genes in this cohort were TP53 (41.27%, 26/63), KRAS (31.75%, 20/63), ARID1A and IDH1 (15.87%, 10/63, for both), SMAD4 (14.29%, 9/63), FGFR2 and BAP1 (12.70%, 8/63, for both), and CDKN2A (11.11%, 7/63). BAP1 mutations were significantly correlated with the CCA subtype. LRP2 mutations were significantly associated with the younger intrahepatic CCA (iCCA) patients, while BAP1 was associated with iCCA patients aged 55-65 years old. BAP1 and LRP2 mutations were associated with TMB. CONCLUSIONS: Most Chinese CCA patients were 50-70 years old. BAP1 and LRP2 mutations were associated with the age of iCCA patients.
OBJECTIVE:Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Here, we aimed to identify the genomic profile of CCA and provided molecular evidence for further biomarker development. METHODS: The formalin-fixed paraffin-embedded and matching blood samples were sequenced by deep sequencing targeting 450 cancer genes and genomic alteration analysis was performed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most commonly altered genes in this cohort were TP53 (41.27%, 26/63), KRAS (31.75%, 20/63), ARID1A and IDH1 (15.87%, 10/63, for both), SMAD4 (14.29%, 9/63), FGFR2 and BAP1 (12.70%, 8/63, for both), and CDKN2A (11.11%, 7/63). BAP1 mutations were significantly correlated with the CCA subtype. LRP2 mutations were significantly associated with the younger intrahepatic CCA (iCCA) patients, while BAP1 was associated with iCCA patients aged 55-65 years old. BAP1 and LRP2 mutations were associated with TMB. CONCLUSIONS: Most Chinese CCA patients were 50-70 years old. BAP1 and LRP2 mutations were associated with the age of iCCA patients.