Histotype-specific copy-number alterations in ovarian cancer

Ruby YunJu Huang, Geng Bo Chen, Noriomi Matsumura, Hung Cheng Lai, Seiichi Mori, Jingjing Li, Meng Kang Wong, Ikuo Konishi, Jean Paul Thiery, Liang K. Goh

研究成果: 雜誌貢獻文章

26 引文 (Scopus)

摘要

Background: Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses. Methods: To dissect the heterogeneity of ovarian cancer and identify histotypes-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer. Results: In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6%) but deleted in serous tumors (15.1%). Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007). There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors. Conclusions: The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.
原文英語
頁(從 - 到)47
頁數1
期刊BMC Medical Genomics
5
DOIs
出版狀態接受/付印 - 十月 18 2012
對外發佈Yes

指紋

Ovarian Neoplasms
Neoplasms
Mutation
Neoplasm Genes
Computer Simulation
Sample Size
Drug Therapy
Growth
Genes
Ovarian epithelial cancer

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

引用此文

Huang, R. Y., Chen, G. B., Matsumura, N., Lai, H. C., Mori, S., Li, J., ... Goh, L. K. (認可的出版社/出版中). Histotype-specific copy-number alterations in ovarian cancer. BMC Medical Genomics, 5, 47. https://doi.org/10.1186/1755-8794-5-47

Histotype-specific copy-number alterations in ovarian cancer. / Huang, Ruby YunJu; Chen, Geng Bo; Matsumura, Noriomi; Lai, Hung Cheng; Mori, Seiichi; Li, Jingjing; Wong, Meng Kang; Konishi, Ikuo; Thiery, Jean Paul; Goh, Liang K.

於: BMC Medical Genomics, 卷 5, 18.10.2012, p. 47.

研究成果: 雜誌貢獻文章

Huang, RY, Chen, GB, Matsumura, N, Lai, HC, Mori, S, Li, J, Wong, MK, Konishi, I, Thiery, JP & Goh, LK 2012, 'Histotype-specific copy-number alterations in ovarian cancer', BMC Medical Genomics, 卷 5, 頁 47. https://doi.org/10.1186/1755-8794-5-47
Huang, Ruby YunJu ; Chen, Geng Bo ; Matsumura, Noriomi ; Lai, Hung Cheng ; Mori, Seiichi ; Li, Jingjing ; Wong, Meng Kang ; Konishi, Ikuo ; Thiery, Jean Paul ; Goh, Liang K. / Histotype-specific copy-number alterations in ovarian cancer. 於: BMC Medical Genomics. 2012 ; 卷 5. 頁 47.
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abstract = "Background: Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses. Methods: To dissect the heterogeneity of ovarian cancer and identify histotypes-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer. Results: In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6{\%}) but deleted in serous tumors (15.1{\%}). Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007). There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors. Conclusions: The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.",
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T1 - Histotype-specific copy-number alterations in ovarian cancer

AU - Huang, Ruby YunJu

AU - Chen, Geng Bo

AU - Matsumura, Noriomi

AU - Lai, Hung Cheng

AU - Mori, Seiichi

AU - Li, Jingjing

AU - Wong, Meng Kang

AU - Konishi, Ikuo

AU - Thiery, Jean Paul

AU - Goh, Liang K.

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Y1 - 2012/10/18

N2 - Background: Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses. Methods: To dissect the heterogeneity of ovarian cancer and identify histotypes-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer. Results: In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6%) but deleted in serous tumors (15.1%). Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007). There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors. Conclusions: The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.

AB - Background: Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses. Methods: To dissect the heterogeneity of ovarian cancer and identify histotypes-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer. Results: In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6%) but deleted in serous tumors (15.1%). Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007). There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors. Conclusions: The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.

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