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Updated: Aug 8, 2026
Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
Molecular characterization of gallbladder cancer using somatic mutation profiling
Milind Javle1, Asif Rashid1, Chaitanya Churi1
1The University of Texas M.D. Anderson Cancer Center, Houston, TX,77054, USA.
Abstract:
Gallbladder cancer is relatively uncommon, with a high incidence in certain geographic locations, including Latin America, East and South Asia, and Eastern Europe. Molecular characterization of this disease has been limited, and targeted therapy options for advanced disease remain an open area of investigation. In the present study, surgical pathology obtained from resected gallbladder cancer cases (n = 72) was examined for the presence of targetable, somatic mutations. All cases were formalin fixed and paraffin embedded (FFPE). Two approaches were used: (a) mass spectroscopy-based profiling for 159 point ("hot spot") mutations in 33 genes commonly involved in solid tumors and (b) next-generation sequencing (NGS) platform that examined the complete coding sequence of in 182 cancer-related genes. Fifty-seven cases were analyzed for hot spot mutations; and 15, for NGS. Fourteen hot spot mutations were identified in 9 cases. Of these, KRAS mutation was significantly associated with poor survival on multivariate analysis. Other targetable mutations included PIK3CA (n = 2) and ALK (n = 1). On NGS, 26 mutations were noted in 15 cases. TP53 and PI3 kinase pathway (STK11, RICTOR, TSC2) mutations were common. One case had FGF10 amplification, whereas another had FGF3-TACC gene fusion, not previously described in gallbladder cancer. In conclusion, somatic mutation profiling using archival FFPE samples from gallbladder cancer is feasible. NGS, in particular, may be a useful platform for identifying novel mutations for targeted therapy.
Insights
Molecular profiling of gallbladder cancer (GBC) identified targetable mutations, including KRAS, which correlated with poor survival. Next-generation sequencing (NGS) is a feasible approach for discovering novel mutations for advanced GBC targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gallbladder cancer (GBC) is uncommon globally but has high incidence in specific regions.
- Limited molecular characterization hinders targeted therapy development for advanced GBC.
Purpose of the Study:
- To investigate targetable somatic mutations in gallbladder cancer using archival samples.
- To assess the feasibility of molecular profiling for identifying therapeutic targets.
Main Methods:
- Surgical pathology from 72 GBC cases (formalin-fixed, paraffin-embedded) were analyzed.
- Two methods were employed: mass spectroscopy for 159 hotspot mutations in 33 genes, and next-generation sequencing (NGS) for 182 cancer-related genes.
- Fifty-seven cases underwent hotspot mutation analysis, and 15 underwent NGS.
Main Results:
- Fourteen hotspot mutations were found in 9 cases; KRAS mutations were linked to poorer survival.
- NGS identified 26 mutations in 15 cases, with common TP53 and PI3 kinase pathway alterations.
- Novel findings included FGF10 amplification and an FGF3-TACC gene fusion in GBC.
Conclusions:
- Somatic mutation profiling of GBC using archival FFPE samples is achievable.
- NGS is a valuable tool for identifying novel mutations and potential targeted therapies in GBC.
- Further research into these mutations may lead to improved GBC treatment strategies.
