Project description:The study involves targeted sequencing of 30 orphan FFPE tumors obtained from anaplastic thyroid carcinoma patients of Indian origin. With this, we aim to describe the mutation profile of this specific subset of anaplastic thyroid cancer patients. This knowledge will further allow us to gain an insight into genomic alterations prevalent in Indian anaplastic thyroid carcinoma.
Project description:The study involves whole exome sequencing of 38 orphan primary tumors obtained from anaplastic thyroid carcinoma patients of Indian origin. With this, we aim to describe the mutational profile of this specific subset of anaplastic thyroid cancer patients. This knowledge will further allow us to gain an insight into potentially actionable genomic alterations prevalent in Indian anaplastic thyroid carcinoma.
Project description:The study involves whole transcriptome sequencing of 30 orphan FFPE tumors obtained from anaplastic thyroid carcinoma patients of Indian origin. With this, we aim to describe the expression profile, fusion genes and pathogen profile of this specific subset of anaplastic thyroid cancer patients. This knowledge will further allow us to gain an insight into transcriptomic alterations prevalent in Indian anaplastic thyroid carcinoma.
Project description:The study involves whole transcriptome sequencing of 40 orphan FFPE tumors obtained from papillary thyroid carcinoma patients of Indian origin. With this, we aim to describe the expression profile, fusion genes and pathogen profile of this specific subset of papillary thyroid cancer patients. This knowledge will further allow us to gain an insight into transcriptomic alterations prevalent in Indian papillary thyroid carcinoma.
Project description:Purpose: The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. The development of new and effective treatment has been and continues to be a major public health imperative. Methods: We report mutational and copy number analysis of 44 predominantly early-staged gallbladder tumors and 5-gallbladder cancer cell lines by a combination of directed and whole exome sequencing at an average coverage of 100X and above. Using gallbladder cancer cell lines and xenograft mouse models we performed phospho-proteome array profiling, followed by an in-depth functional characterization. Results: We describe recurrent activating ERBB2 somatic mutation in 6 of 44 gallbladder primary tumors with an overall mutation frequency of 13%, along with KRAS activating mutations in 3 of 44 samples. Consistent with whole exome findings, a phospho-proteomic array profile of 49-tyrosine kinase revealed constitutive phosphorylation of ERBB2 and EGFR that were found to heterodimerize. We demonstrate that treatment with ERBB2-specific, EGFR-specific shRNA or with covalent EGFR family inhibitor BIBW-2992 inhibits transformation, survival, migration, invasion, and tumor forming characteristics of gallbladder cancer cells harboring wild type or KRAS (G13D) but not KRAS (G12V) mutation. Furthermore, we show in vivo reduction in tumor size is paralleled by a reduction in the amounts of phospho-ERK in KRAS (G13D) but not in KRAS (G12V) xenografts, validating the in vitro findings Conclusion: Findings from this study implicate ERBB2 as an important therapeutic target in early stage gallbladder cancer. We also present the first evidence that the presence of KRAS (G12V), but not KRAS (G13D) mutation, may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to the clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.
Project description:Whole exome sequencing was performed on set of 48 DNA samples obtained from 16 EGFR mutated NSCLC patients whose tumors progressed following EGFR-TKI treatment. The DNA samples included baseline biopsy, rebiopsy and blood from the same patient. By comparing the variants in rebiopsy tumors and baseline tumors we aim to understand the genomic alterations responsible for the development of EGFR-TKI resistance in NSCLC patients.