In past reporting periods, we procured a series of primary endometrial carcinosarcomas and paired non-tumor tissues through the Cooperative Human Tissue Network, which is supported by the National Cancer Institute. During the current reporting period, we isolated DNAs from these tissues. The paired tumor-normal DNAs are currently undergoing identity testing to ensure they are consistent with being derived from the same individual. We anticipate submitting the DNAs to the NIH intramural sequencing center for whole exome sequencing within the final quarter of this reporting period. During the next reporting period we plan to: (1) Curate and filter the exome sequence data to distinguish germline variants (present in both tumor and normal DNAs) from somatic variants (present exclusively in the tumor DNA). (2) Subject the somatic variants to orthogonal validation, using Sanger sequencing and/or mass spectrometry, to distinguish true somatic mutations from false-positive calls. (3) Resequence frequently mutated genes, or genes that form frequently mutated biochemical pathways or biological processes, from a larger set of primary endometrial carcinomas. (4) Continue to procure additional anonymized, endometrial carcinosarcomas and matched normal tissues for use in the proposed studies.
