Abstract 2191: Development of a phylogenetic tree model to investigate the role of genetic mutations in a single endometrial tumor

Modern genome sequencing technology has identified thousands of mutations in human tumors, but analysis of the role of genetic mutations in tumor development, utilizing prevalence information from many tumors, has yet to define in patients the functional contribution of genetic mutations, individually and collectively. To understand the genetic basis of human endometrial cancer, the fourth most common cancer in women, transcriptome sequencing was performed on an endometrial tumor paired with normal cervical tissue, and 26 non-synonymous somatic mutations were confirmed in the tumor genome DNA. A phylogenetic tree illustrating the mutational timeline was developed based upon the distribution of 26 mutations in 30 randomly-selected laser-captured single cells from the tumor sections. Five ubiquitous mutations were identified that are presumed to occur in the cancer founder cell of the tumor, which may collectively play critical roles in endometrial oncogenesis. However, further testing in 10 additional endometrial tumors failed to show overlapping mutations, indicating the lack of a single common oncogenic pathway for these endometrial tumors.

Furthermore, we developed a mathematical and phylogenetic calculation of the cell population produced by a mutated ancestor cell, which quantifies the role of tumor-specific individual genetic mutations in cancer cell proliferation in a single resected patient tumor, without relying on prevalence information from other patients. This novel approach will be further tested in a larger sample set to determine whether multiple genetic mutations’ quantitative contributions can be used to predict patient outcomes.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2191.