المؤلفون: Navneet Sangha, Rong Wu, Rork Kuick, Scott Powers, David Mu, Diane Fiander, Kit Yuen, Hidetaka Katabuchi, Hironori Tashiro, Eric R. Fearon, Kathleen R. Cho

المصدر: Neoplasia: An International Journal for Oncology Research, Vol 10, Iss 12, Pp 1362-1372 (2008)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Ovarian serous carcinoma (OSC) is the most common and lethal histologic type of ovarian epithelial malignancy. Mutations of TP53 and dysfunction of the Brca1 and/or Brca2 tumor-suppressor proteins have been implicated in the molecular pathogenesis of a large fraction of OSCs, but frequent somatic mutations in other well-established tumor-suppressor genes have not been identified. Using a genome-wide screen of DNA copy number alterations in 36 primary OSCs, we identified two tumors with apparent homozygous deletions of the NF1 gene. Subsequently, 18 ovarian carcinoma-derived cell lines and 41 primary OSCs were evaluated for NF1 alterations. Markedly reduced or absent expression of Nf1 protein was observed in 6 of the 18 cell lines, and using the protein truncation test and sequencing of cDNA and genomic DNA, NF1 mutations resulting in deletion of exons and/or aberrant splicing of NF1 transcripts were detected in 5 of the 6 cell lines with loss of NF1 expression. Similarly, NF1 alterations including homozygous deletions and splicing mutations were identified in 9 (22%) of 41 primary OSCs. As expected, tumors and cell lines with NF1 defects lacked mutations in KRAS or BRAF but showed Ras pathway activation based on immunohistochemical detection of phosphorylated MAPK (primary tumors) or increased levels of GTP-bound Ras (cell lines). The TP53 tumor-suppressor gene was mutated in all OSCs with documented NF1 mutation, suggesting that the pathways regulated by these two tumor-suppressor proteins often cooperate in the development of ovarian carcinomas with serous differentiation.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1476558608800814Test; https://doaj.org/toc/1476-5586Test; https://doaj.org/toc/1522-8002Test

الوصول الحر: https://doaj.org/article/5f0eb8adf4a54d7b950214b03e698f90Test

المؤلفون: Rong Wu, Denise C. Connolly, Xiaodan Ren, Eric R. Fearon, Kathleen R. Cho

المصدر: Neoplasia: An International Journal for Oncology Research, Vol 1, Iss 4, Pp 311-314 (1999)

مصطلحات موضوعية: tumor suppressor gene, human chromosome 11, loss of heterozygosity, ovarian carcinoma, PPP2R1B, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Previous studies have demonstrated frequent allelic losses of distal chromosome 11q in ovarian carcinomas. The tumor suppressor gene(s) presumably targeted by these losses have not yet been identified. PPP2R1B is a candidate tumor suppressor gene at 11q23 that has recently been shown to be mutated in a subset of colorectal and lung cancers. We evaluated 5 ovarian carcinoma cell lines and 27 primary ovarian carcinomas for allelic losses of 11q23 and for mutations in the open reading frame of PPP2R1B. We also evaluated the primary tumors for allelic losses at 17p13, another chromosomal region frequently affected by losses of heterozygosity (LOH) in ovarian cancers. 11q23 and 17p13 allelic losses were identified in 25% and 74% of the carcinomas, respectively. No mutations within PPP2R1Bcoding sequences were found. These findings indicate that mutations of the PPP2R1B gene are infrequent in ovarian cancer and that deletions affecting the distal portion of chromosome 11q in ovarian cancer likely target inactivation of other genes.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1476558699800219Test; https://doaj.org/toc/1476-5586Test; https://doaj.org/toc/1522-8002Test

الوصول الحر: https://doaj.org/article/3b1ea63573394e8d927380de53dde8adTest

المؤلفون: Ian Beddows, Huihui Fan, Karolin Heinze, Benjamin K. Johnson, Anna Leonova, Janine Senz, Svetlana Djirackor, Kathleen R. Cho, Celeste Leigh Pearce, David G. Huntsman, Michael S. Anglesio, Hui Shen

مصطلحات موضوعية: Cancer, Cancer Risk Factors, Cancer Biology, Molecular and Cellular Biology, Therapeutic Research and Development, Carcinogenesis, Tumor initiation and promotion, Drug Targets, Epigenetics, Gynecological Cancers, Ovarian cancer

الوصف: Figures S1-S5

العلاقة: https://figshare.com/articles/journal_contribution/Supplementary_Data_from_Cell_State_of_Origin_Impacts_Development_of_Distinct_Endometriosis-Related_Ovarian_Carcinoma_Histotypes/24924089Test

الإتاحة: https://doi.org/10.1158/0008-5472.24924089.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Data_from_Cell_State_of_Origin_Impacts_Development_of_Distinct_Endometriosis-Related_Ovarian_Carcinoma_Histotypes/24924089Test

المؤلفون: Ian Beddows, Huihui Fan, Karolin Heinze, Benjamin K. Johnson, Anna Leonova, Janine Senz, Svetlana Djirackor, Kathleen R. Cho, Celeste Leigh Pearce, David G. Huntsman, Michael S. Anglesio, Hui Shen

مصطلحات موضوعية: Cancer, Cancer Risk Factors, Cancer Biology, Molecular and Cellular Biology, Therapeutic Research and Development, Carcinogenesis, Tumor initiation and promotion, Drug Targets, Epigenetics, Gynecological Cancers, Ovarian cancer

الوصف: Supplementary Tables S1-10

العلاقة: https://figshare.com/articles/dataset/Supplementary_Tables_S1-10_from_Cell_State_of_Origin_Impacts_Development_of_Distinct_Endometriosis-Related_Ovarian_Carcinoma_Histotypes/24924086Test

الإتاحة: https://doi.org/10.1158/0008-5472.24924086.v1Test
https://figshare.com/articles/dataset/Supplementary_Tables_S1-10_from_Cell_State_of_Origin_Impacts_Development_of_Distinct_Endometriosis-Related_Ovarian_Carcinoma_Histotypes/24924086Test

المؤلفون: Scott A. Tomlins, Andrew P. Sciallis, Kathleen R. Cho, Cody S. Carter, Chia-Jen Liu, Daniel H. Hovelson, Javed Siddiqui, Nolan R. Bick, Kevin Hu, Mia C. Samaha, Lorena Lazo de la Vega

الوصف: The molecular events driving low-grade endometrioid endometrial carcinoma (LGEC) development—like in many cancers—are incompletely understood. Hence, here we performed multiregion, comprehensive somatic molecular profiling of routinely processed formalin-fixed, paraffin-embedded (FFPE) material from 13 cases of LGEC totaling 64 minute, spatially defined cell populations ranging from presumed precursor lesions through invasive LGEC. Shared driving PTEN, PIK3R1, or PIK3CA mutations support clonal origin of the samples in each case, except for two cases with two clonally distinct neoplastic populations, consistent with unexpected multiclonality in LGEC development. Although substantial heterogeneity in driving somatic alterations was present across populations in nearly all cases, these alterations were usually clonal in a given population, supporting continued selection and clonal sweeping of driving alterations in populations with both precursor and LGEC histology. Importantly, CTNNB1 mutational status, which has been proposed as both prognostic and predictive in LGEC, was frequently heterogeneous and subclonal, occurring both exclusively in precursor or cancer populations in different cases. Whole-transcriptome profiling of coisolated RNA from 12 lesions (from 5 cases) was robust and confirmed histologic and molecular heterogeneity, including activated Wnt signaling in CTNNB1-mutant versus wild-type populations. Taken together, we demonstrate clinically relevant multiclonality and intratumoral heterogeneity during LGEC development with important implications for diagnosis, prognosis, and therapeutic prediction. More broadly, our methodology is broadly scalable to enable high-throughput genomic and transcriptomic characterization of precursor and invasive cancer populations from routine FFPE specimens.Implications:Multiregion profiling of LGEC populations using a highly scalable approach demonstrates clinically relevant multiclonality and intratumoral heterogeneity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6bf75cdd33d3fd4cad10dba1ae3998bfTest
https://doi.org/10.1158/1541-7786.c.6541149Test

المؤلفون: Ronald J. Buckanovich, Kathleen R. Cho, Euisik Yoon, Moshe Talpaz, Yu-Chih Chen, Karen McLean, Rong Wu, Daniela Burgos-Ojeda

الوصف: Supplemental Figure 3. Stem cell gene expression in CD24+ and CD24- cells and CD44+ and CD44- cells

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a4bc0df04000801876fa18e87bda6ceTest
https://doi.org/10.1158/1535-7163.22502470Test

المؤلفون: Ronald J. Buckanovich, Kathleen R. Cho, Euisik Yoon, Moshe Talpaz, Yu-Chih Chen, Karen McLean, Rong Wu, Daniela Burgos-Ojeda

الوصف: Supplemental Figure 1. Bioluminescent images of cancer stem cell markers evaluated

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03ab53a81875585b3a766e630255d6dbTest
https://doi.org/10.1158/1535-7163.22502476.v1Test

المؤلفون: Ronald J. Buckanovich, Kathleen R. Cho, Euisik Yoon, Moshe Talpaz, Yu-Chih Chen, Karen McLean, Rong Wu, Daniela Burgos-Ojeda

الوصف: Supplemental Figure 5. FACS isolation strategy and purity of sort

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33ed4ea824b242f0fcc1dcfed2e414b1Test
https://doi.org/10.1158/1535-7163.22502464.v1Test

المؤلفون: Scott A. Tomlins, Andrew P. Sciallis, Kathleen R. Cho, Cody S. Carter, Chia-Jen Liu, Daniel H. Hovelson, Javed Siddiqui, Nolan R. Bick, Kevin Hu, Mia C. Samaha, Lorena Lazo de la Vega

الوصف: Supplementary Methods, Figure Legends, Figures 1 - 9, Tables 1 - 8 from Multiclonality and Marked Branched Evolution of Low-Grade Endometrioid Endometrial Carcinoma

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a1d04aba367407bd8030f60b0502a0bTest
https://doi.org/10.1158/1541-7786.22515636Test

المؤلفون: Ronald J. Buckanovich, Kathleen R. Cho, Euisik Yoon, Moshe Talpaz, Yu-Chih Chen, Karen McLean, Rong Wu, Daniela Burgos-Ojeda

الوصف: Supplemental Figure 2. FACS analysis of CD24 and CD133 expression of CD24+ or CD24- tumors

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::32279cafb9cfd9e7217b244b705355a8Test
https://doi.org/10.1158/1535-7163.22502473.v1Test