Personalized oncogenomics in the management of gastrointestinal carcinomas-early experiences from a pilot study
B S Sheffield1, B Tessier-Cloutier1, H Li-Chang2
1Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC.
Background:
Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways.
Methods:
We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma.
Results:
In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation; and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators.
Summary:
We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.
Insights
Whole-genome and transcriptome sequencing rapidly identify actionable mutations in complex gastrointestinal cancers. This genomic profiling aids in diagnosing unknown primaries and guiding targeted therapies for metastatic disease.
Area of Science:
- Genomic medicine
- Oncology
- Cancer genomics
Background:
- Gastrointestinal carcinomas are complex, lethal metastatic cancers.
- Whole-genome and transcriptome sequencing enable simultaneous characterization of oncogenic pathways.
Purpose of the Study:
- To demonstrate the clinical utility of rapid whole-genome and transcriptome sequencing in managing metastatic gastrointestinal carcinomas.
- To showcase the application of genomic profiling in diagnosing unknown primary tumors and guiding targeted therapies.
Main Methods:
- Real-time genomic profiling of metastatic gastrointestinal carcinoma patients within the Personalized Onco-Genomics program.
- Integration of clinical expertise with genomic data for diagnosis and treatment strategy.
- Case studies involving carcinoma of unknown primary, colorectal cancer, and appendiceal adenocarcinoma.
Main Results:
- Identified IDH1 mutation and EGFR amplification in an unknown primary, aiding cholangiocarcinoma diagnosis and therapy.
- Detected BRAF V600E mutation in colorectal cancer, supporting targeted therapy.
- Characterized appendiceal adenocarcinoma with p53 inactivation and activated signaling pathways.
Conclusions:
- Whole-genome and transcriptome sequencing are achievable within clinically effective timelines.
- Genomic sequencing provides clinically useful and actionable information for complex cancers.
- This approach facilitates precise diagnosis and personalized treatment strategies.
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