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Targeted deep sequencing of solid tumors to predict response to therapy: A study in an Indian population.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Massively parallel deep sequencing of genes involved in cancer can provide a comprehensive understanding of the processes that drive an individual's cancer and potentially provide personalized therapy options. Single gene sequencing based tests may provide an incomplete understanding of oncogenic pathways and response to therapy. We evaluated the utility of an NGS-multi-gene panel based approach in impacting treatment in a wide range of solid tumors from an Indian population of patients Methods: DNA from saliva and FFPE blocks of 30 tumor samples from varied tissue types (lung, colon, breast, ovary, glioblastoma, head and neck) was taken from consenting patients and subjected to deep sequencing using Illumina’s TSCAP 48 gene panel and the MiSeq technology. The average coverage across 220 hot spots was greater than 1000X in each sample. Data was processed using Avadis NGS™. Mutations identified in the tumor but not in the paired normal DNA were assessed for ‘actionability’ i.e. impact on prognosis and response to therapy. Results: Differential somatic alterations in the tumor were detected in 90% of the cases with TP53 being most frequently mutated. In half of the cases, variants were found with possible impact on prognosis or therapy. Notably, in 30% of the cases, somatic variants directly impacting therapy were found in genes encoding members in the growth factor signaling pathway. Variants with therapeutic relevance were found in PIK3CA, PTEN, KRAS and NRAS. Of these, variants in PIK3CA were the most frequent. Standard single gene testing would have identified only one KRASvariant. All the variants identified indicated resistance to conventional therapy (such as anti-EGFR, or anti-ERBB2) and suggested sensitivity to alternative targeted therapy, either approved or in clinical trials. These results thus have the potential to alter the course of therapy for these patients and open up new options of treatment. Conclusions: Our data from this pilot study suggest that targeted deep sequencing using a multi-gene panel approach can yield useful therapeutic insights in a wide range of tumor types. Ongoing work is aimed at expanding the range of genes examined in this test so as to increase therapeutic impact.
Abstracts by Urvashi Bahadur:
- Meeting: 2015 ASCO Annual Meeting | Abstract No: e12539
Clinical utility of PI3K/AKT/mTOR pathway activation in breast cancer: A study in Indian population.Meeting: 2015 ASCO Annual Meeting | Abstract No: e12542
Clinical utility of profiling somatic alterations in Indian cancer patients using a multi-gene next generation sequencing (NGS) test.Meeting: 2015 ASCO Annual Meeting | Abstract No: e22127