Landscape of Targetable Genetic Alterations in Advanced Cholangiocarcinoma among Patients in Southeast Asia

• Bhavisha Patel

  Sumandeep Nursing College, Sumandeep Vidyapeeth (Deemed to be University), Vadodara, Gujarat, India

• Balasankar Karavadi

  Department of Bioinformatics, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India

• Ravindrasinh M. Rajput

  Faculty of Allied and Healthcare, Gokul Global University, Sidhpur, Gujarat, India

• Shivangi Gupta

  Quantum University Research Center, Quantum University, Roorkee, Uttarakhand, 247667, India

• Rajashree Panigrahi

  Department of Microbiology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India

• P. Ravishankar

  Department of General Surgery, Vinayaka Mission’s Kirupananda Variyar Medical College & Hospitals Vinayaka Mission’s Research Foundation (DU), Salem, Tamil Nadu, India

• Saksham Sood

  Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India

• Honganur Raju Manjunath

  Department of Physics, Faculty of Engineering and Technology, JAIN (Deemed-to-be University), Bengaluru, Karnataka, India

Cholangiocarcinoma (CCA) is a heterogeneous form of biliary tract cancer, for which treatment options remain limited; however, molecular profiling technology has helped in uncovering genomic mutations that can be used in precision oncology. This molecular profiling study has been carried out retrospectively in order to investigate the genomic alterations that are targetable in advanced cholangiocarcinomas of Southeast Asia. Samples from 126 patients were analyzed through targeted next generation sequencing in order to identify somatic mutations, copy number alterations, and gene fusions. Identified genomic alterations were characterized based on their clinical relevance and relation with biomarker-based treatment. A potentially actionable genomic alteration was observed in 93 patients (73.8%), while 28 patients (22.2%) had multiple genomic alterations. The commonest observed alterations consisted of mutations in TP53 (19.0%), fusion events of FGFR2 (16.7%), mutations in IDH1 (14.3%), mutations in KRAS (13.5%), and amplifications of ERBB2 (7.1%). This indicates the presence of considerable molecular diversity among patients with advanced cholangiocarcinoma and the existence of genomic subtypes that have clinical relevance in the Southeast Asian population. The detection of actionable genomic alterations among patients provides clear evidence on the need for genomic profiling as a strategy for molecular characterization and testing of biomarkers. Prospective multicentre studies will be necessary to confirm the results.

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