Publications by authors named "Danushka Galappaththige"
The application of paired-end next generation sequencing approaches has made it possible to systematically characterize rearrangements of the cancer genome to base-pair level. Utilizing this approach, we report the first detailed analysis of ovarian cancer rearrangements, comparing high-grade serous and clear cell cancers, and these histotypes with other solid cancers. Somatic rearrangements were systematically characterized in eight high-grade serous and five clear cell ovarian cancer genomes and we report here the identification of > 600 somatic rearrangements.
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- The genetics of renal cancer, particularly clear cell carcinoma (ccRCC), is largely influenced by the inactivation of the VHL tumor suppressor gene.
- Recent research identified new cancer-related genes in ccRCC, including UTX, JARID1C, and SETD2, which are involved in modifying histone H3 methylation that affects gene expression.
- The study also found that mutations in the PBRM1 gene, part of the SWI/SNF chromatin remodeling complex, occur in 41% of ccRCC cases, highlighting the importance of chromatin biology in this type of cancer.
Background: Here we present the first paired-end sequencing of tumors from genetically engineered mouse models of cancer to determine how faithfully these models recapitulate the landscape of somatic rearrangements found in human tumors. These were models of Trp53-mutated breast cancer, Brca1- and Brca2-associated hereditary breast cancer, and E-cadherin (Cdh1) mutated lobular breast cancer.
Results: We show that although Brca1- and Brca2-deficient mouse mammary tumors have a defect in the homologous recombination pathway, there is no apparent difference in the type or frequency of somatic rearrangements found in these cancers when compared to other mouse mammary cancers, and tumors from all genetic backgrounds showed evidence of microhomology-mediated repair and non-homologous end-joining processes.