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Amplification of The ch19p13.2 NACC1 Locus in Ovarian High-grade Serous Carcinoma

Based on digital karyotyping, we have identified a new, discrete amplified region at ch19p13.2 in a high-grade ovarian serous carcinoma. To further characterize this region, we determined the frequency and biological significance of ch19p13.2 amplification by analyzing 341 high-grade serous carcinom...

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Autores principales: Shih, Ie-Ming, Nakayama, Kentaro, Wu, Gang, Nakayama, Naomi, Zhang, Jinghui, Wang, Tian-Li
Formato: Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085564/
https://www.ncbi.nlm.nih.gov/pubmed/21240255
http://dx.doi.org/10.1038/modpathol.2010.230
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author Shih, Ie-Ming
Nakayama, Kentaro
Wu, Gang
Nakayama, Naomi
Zhang, Jinghui
Wang, Tian-Li
author_facet Shih, Ie-Ming
Nakayama, Kentaro
Wu, Gang
Nakayama, Naomi
Zhang, Jinghui
Wang, Tian-Li
author_sort Shih, Ie-Ming
collection PubMed
description Based on digital karyotyping, we have identified a new, discrete amplified region at ch19p13.2 in a high-grade ovarian serous carcinoma. To further characterize this region, we determined the frequency and biological significance of ch19p13.2 amplification by analyzing 341 high-grade serous carcinomas from The Cancer Genome Atlas (TCGA) and found an increased DNA copy number at this locus in 18% of cases. We correlated the DNA and RNA copy number by analyzing the TCGA dataset for all amplified genes and detected 7 genes within ch19p13.2 that were significantly correlated (R ≥0.54) and were, in fact, listed as the top 100 potential “driver” genes at a genome-wide scale. Interestingly, one of the 7 genes, NACC1, encoding NAC1 was previously reported to be involved in the development of tumor recurrence in ovarian serous carcinoma and to play a causal role in the development of paclitaxel resistance. Therefore, we selected NACC1 for validation in an independent cohort. Based on fluorescence in situ hybridization, we found that 35 (20%) of 175 high-grade serous carcinomas had an increased DNA copy number at the NACC1 locus, and those amplified cases were associated with early disease recurrence within 6 months (p= 0.013). A significantly high level of NAC1 protein expression based on immunohistochemistry was detected in amplified tumors as compared to non-amplified tumors (p< 0.005). In summary, our data suggest that amplification at the ch19p13.2 NACC1 locus, leading to NAC1 overexpression, is one of the molecular genetic alterations associated with early tumor recurrence in ovarian cancer.
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spelling pubmed-30855642011-11-01 Amplification of The ch19p13.2 NACC1 Locus in Ovarian High-grade Serous Carcinoma Shih, Ie-Ming Nakayama, Kentaro Wu, Gang Nakayama, Naomi Zhang, Jinghui Wang, Tian-Li Mod Pathol Article Based on digital karyotyping, we have identified a new, discrete amplified region at ch19p13.2 in a high-grade ovarian serous carcinoma. To further characterize this region, we determined the frequency and biological significance of ch19p13.2 amplification by analyzing 341 high-grade serous carcinomas from The Cancer Genome Atlas (TCGA) and found an increased DNA copy number at this locus in 18% of cases. We correlated the DNA and RNA copy number by analyzing the TCGA dataset for all amplified genes and detected 7 genes within ch19p13.2 that were significantly correlated (R ≥0.54) and were, in fact, listed as the top 100 potential “driver” genes at a genome-wide scale. Interestingly, one of the 7 genes, NACC1, encoding NAC1 was previously reported to be involved in the development of tumor recurrence in ovarian serous carcinoma and to play a causal role in the development of paclitaxel resistance. Therefore, we selected NACC1 for validation in an independent cohort. Based on fluorescence in situ hybridization, we found that 35 (20%) of 175 high-grade serous carcinomas had an increased DNA copy number at the NACC1 locus, and those amplified cases were associated with early disease recurrence within 6 months (p= 0.013). A significantly high level of NAC1 protein expression based on immunohistochemistry was detected in amplified tumors as compared to non-amplified tumors (p< 0.005). In summary, our data suggest that amplification at the ch19p13.2 NACC1 locus, leading to NAC1 overexpression, is one of the molecular genetic alterations associated with early tumor recurrence in ovarian cancer. 2011-01-14 2011-05 /pmc/articles/PMC3085564/ /pubmed/21240255 http://dx.doi.org/10.1038/modpathol.2010.230 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shih, Ie-Ming
Nakayama, Kentaro
Wu, Gang
Nakayama, Naomi
Zhang, Jinghui
Wang, Tian-Li
Amplification of The ch19p13.2 NACC1 Locus in Ovarian High-grade Serous Carcinoma
title Amplification of The ch19p13.2 NACC1 Locus in Ovarian High-grade Serous Carcinoma
title_full Amplification of The ch19p13.2 NACC1 Locus in Ovarian High-grade Serous Carcinoma
title_fullStr Amplification of The ch19p13.2 NACC1 Locus in Ovarian High-grade Serous Carcinoma
title_full_unstemmed Amplification of The ch19p13.2 NACC1 Locus in Ovarian High-grade Serous Carcinoma
title_short Amplification of The ch19p13.2 NACC1 Locus in Ovarian High-grade Serous Carcinoma
title_sort amplification of the ch19p13.2 nacc1 locus in ovarian high-grade serous carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085564/
https://www.ncbi.nlm.nih.gov/pubmed/21240255
http://dx.doi.org/10.1038/modpathol.2010.230
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