Project description:A 58 year old female diagnosed with a metastic GI-NET underwent resection of primary tumor as well as several metastatic lesions. We performed scRNA-seq of the primary tumor and one lesion from the liver metastasis to perform comparitive analysis between the primary and metastic tumor compositions.
Project description:Here we report the RNA sequence of a primary patient-derived xenograft neuroendocrine tumor and compare it to the RNA sequence of an intraperitoneal metastatic tumor that was established using the respective primary tumor. Using this data, we identified key differences that validated the metastatic tumor to indeed have a more mestatic genotype. Noteworthy differences were the upregulation of matrix metalloproteinases and downregulation of PTK2, both associated with metastatic neuroendocrine tumors in patients. Furthermore, we found upregulated pathways that could potentially be targeted through small molecule inhibition. One such example is ERK1/2 had a higher expression in the metastatic tumor and using a MEK inhibitor, were able to successfully deplete metastasis of the tumor in an in vivo model. These data will be helpful in translating the therapeutics tested to a clinical arena.
Project description:Reports on common mutations in neuroendocrine tumors (NET) are rare and clonality of NET metastases has not been investigated in this tumor entity yet. We selected a NET and a the corresponding lymph node and liver metastases as well as the derivative cell lines to screen for somatic mutations in the primary NET and to track the fate of genetic changes (by Affymetrix SNP 6.0 micorarray and targeted resequencing by 454 GS FLX) and during metastasis and in vitro progression. using Affymetrix SNP 6.0 Arrays. Affymetrix SNP 6.0 arrays were performed according to the manufacturer's directions on DNA extracted from cryo material or cell lines. Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 4 samples. 60 samples from HapMap database were used as references for copy number inference.
Project description:Reports on common mutations in neuroendocrine tumors (NET) are rare and clonality of NET metastases has not been investigated in this tumor entity yet. We selected a NET and a the corresponding lymph node and liver metastases as well as the derivative cell lines to screen for somatic mutations in the primary NET and to track the fate of genetic changes (by Affymetrix SNP 6.0 micorarray and targeted resequencing by 454 GS FLX) and during metastasis and in vitro progression. using Affymetrix SNP 6.0 Arrays.
Project description:We analyzed chromatin accessibility, scATAC-seq and RNA-seq across neuroendocrine carcinomas from distinct anatomic origins including Merkel cell carcinomas, neuroendocrine prostate cancer, small cell lung cancer and gastrointestinal NECs.
Project description:We analyzed chromatin accessibility, scATAC-seq and RNA-seq across neuroendocrine carcinomas from distinct anatomic origins including Merkel cell carcinomas, neuroendocrine prostate cancer, small cell lung cancer and gastrointestinal NECs.