Comprehensive analysis of 20q13 genes in ovarian cancer identifies <I>ADRM1</I> as amplification target Export

@article{citeulike:3365516, abstract = {Approximately 25,000 ovarian cancers are diagnosed in the US annually, and 75\% of cases are in the advanced stage when they are largely incurable. There is a critical need for improved early detection tools and development of novel treatments. Because chromosome band 20q13 is a commonly DNA amplified region in ovarian cancer and increase in 20q13 copy number may be an early event, we examined the DNA amplification and RNA expression pattern of 239 microarray probes mapping to this region with the goal of identifying gene(s) associated with ovarian cancer. Using Agilent expression microarray analysis and FISH to tumor tissue arrays, we narrowed the candidates to 19 genes that were consistently overexpressed in a subset of tumors amplified for both ZNF217 and TPD54, although, interestingly the candidates do not include these two amplified genes. Unsupervised clustering of 225 ovarian samples with respect to RNA expression of these 19 genes allowed identification of a 20q-amplified subset of 51 (23\%) tumors and this subset was significantly correlated with poor outcome. Of the 19 candidate genes in this subset, ADRM1 overexpression was the most highly correlated with amplification, was amplified in a higher percentage of tumors than ZNF217 and TPD54, and was significantly upregulated with respect to stage, recurrence and metastasis. In addition, overexpression of ADRM1 correlates significantly with shorter time to recurrence and overall survival. Functional analysis is now warranted to determine whether ADRM1 is a target for early screening and/or therapy for ovarian cancer. {\copyright} 2008 Wiley-Liss, Inc.}, address = {Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA 90095; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Cedars Sinai Medical Center, Los Angeles, CA 90048}, author = {Fejzo, Marlena S. and Dering, Judy and Ginther, Chuck and Anderson, Lee and Ramos, Lilian and Walsh, Christine and Karlan, Beth and Slamon, Dennis J.}, citeulike-article-id = {3365516}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/gcc.20592}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/120748549/ABSTRACT}, doi = {10.1002/gcc.20592}, journal = {Genes, Chromosomes and Cancer}, keywords = {20q, ovarian}, number = {10}, pages = {873--883}, posted-at = {2008-10-02 08:56:44}, priority = {2}, title = {Comprehensive analysis of 20q13 genes in ovarian cancer identifies <I>ADRM1</I> as amplification target}, url = {http://dx.doi.org/10.1002/gcc.20592}, volume = {47}, year = {2008} }

TY - JOUR ID - citeulike:3365516 L3 - citeulike-article-id:3365516 N2 - Approximately 25,000 ovarian cancers are diagnosed in the US annually, and 75% of cases are in the advanced stage when they are largely incurable. There is a critical need for improved early detection tools and development of novel treatments. Because chromosome band 20q13 is a commonly DNA amplified region in ovarian cancer and increase in 20q13 copy number may be an early event, we examined the DNA amplification and RNA expression pattern of 239 microarray probes mapping to this region with the goal of identifying gene(s) associated with ovarian cancer. Using Agilent expression microarray analysis and FISH to tumor tissue arrays, we narrowed the candidates to 19 genes that were consistently overexpressed in a subset of tumors amplified for both ZNF217 and TPD54, although, interestingly the candidates do not include these two amplified genes. Unsupervised clustering of 225 ovarian samples with respect to RNA expression of these 19 genes allowed identification of a 20q-amplified subset of 51 (23%) tumors and this subset was significantly correlated with poor outcome. Of the 19 candidate genes in this subset, ADRM1 overexpression was the most highly correlated with amplification, was amplified in a higher percentage of tumors than ZNF217 and TPD54, and was significantly upregulated with respect to stage, recurrence and metastasis. In addition, overexpression of ADRM1 correlates significantly with shorter time to recurrence and overall survival. Functional analysis is now warranted to determine whether ADRM1 is a target for early screening and/or therapy for ovarian cancer. © 2008 Wiley-Liss, Inc. IS - 10 JF - Genes, Chromosomes and Cancer AD - Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA 90095; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Cedars Sinai Medical Center, Los Angeles, CA 90048 EP - 883 TI - Comprehensive analysis of 20q13 genes in ovarian cancer identifies <I>ADRM1</I> as amplification target VL - 47 SP - 873 KW - 20q KW - ovarian AU - Fejzo, Marlena AU - Dering, Judy AU - Ginther, Chuck AU - Anderson, Lee AU - Ramos, Lilian AU - Walsh, Christine AU - Karlan, Beth AU - Slamon, Dennis PY - 2008/// UR - http://dx.doi.org/10.1002/gcc.20592 ER -