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Title: FAM83 family oncogenes are broadly involved in human cancers: an integrative multi-omics approach

Abstract

The development of novel targeted therapies for cancer treatment requires identification of reliable targets. FAM83 (‘family with sequence similarity 83’) family members A, B, and D were shown recently to have oncogenic potential. However, the overall oncogenic abilities of FAM83 family genes remain largely unknown. Here, we used a systematic and integrative genomics approach to investigate oncogenic properties of the entire FAM83 family members. We assessed transcriptional expression patterns of eight FAM83 family genes (FAM83A-H) across tumor types, the relationship between their expression and changes in DNA copy number, and the association with patient survival. By comparing the gene expression levels of FAM83 family members in cancers from 17 different tumor types with those in their corresponding normal tissues, we identified consistent upregulation of FAM83D and FAM83H across the majority of tumor types, which is largely driven by increased DNA copy number. Importantly, we found also that a higher expression level of a signature of FAM83 family members was associated with poor prognosis in a number of human cancers. In breast cancer, we found that alterations in FAM83 family genes correlated significantly with TP53 mutation, whereas significant, but inverse correlation was observed with PIK3CA and CDH1 (E-cadherin) mutations. We alsomore » identified that expression levels of 55 proteins were significantly associated with alterations in FAM83 family genes including a decrease in GATA3, ESR1, and PGR proteins in tumors with alterations in FAM83. Our results provide strong evidence for a critical role of FAM83 family genes in tumor development, with possible relevance for therapeutic target development.« less

Authors:
 [1];  [1];  [1];  [2];  [1];  [1]
  1. Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, CA USA
  2. Nanjing Biotech and Pharmaceutical Valley Development Center, China
Publication Date:
Research Org.:
Lawrence Berkeley National Lab (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH); National Cancer Institute (NCI)
OSTI Identifier:
1623435
Grant/Contract Number:  
AC02-05CH11231; R01 CA116481
Resource Type:
Accepted Manuscript
Journal Name:
Moletular Oncology
Additional Journal Information:
Journal Volume: 11; Journal Issue: 2; Journal ID: ISSN 1574-7891
Publisher:
Federation of European Biochemical Societies
Country of Publication:
United States
Language:
English
Subject:
Oncology

Citation Formats

Snijders, Antoine M., Lee, Sun-Young, Hang, Bo, Hao, Wenshan, Bissell, Mina J., and Mao, Jian-Hua. FAM83 family oncogenes are broadly involved in human cancers: an integrative multi-omics approach. United States: N. p., 2017. Web. doi:10.1002/1878-0261.12016.
Snijders, Antoine M., Lee, Sun-Young, Hang, Bo, Hao, Wenshan, Bissell, Mina J., & Mao, Jian-Hua. FAM83 family oncogenes are broadly involved in human cancers: an integrative multi-omics approach. United States. https://doi.org/10.1002/1878-0261.12016
Snijders, Antoine M., Lee, Sun-Young, Hang, Bo, Hao, Wenshan, Bissell, Mina J., and Mao, Jian-Hua. Mon . "FAM83 family oncogenes are broadly involved in human cancers: an integrative multi-omics approach". United States. https://doi.org/10.1002/1878-0261.12016. https://www.osti.gov/servlets/purl/1623435.
@article{osti_1623435,
title = {FAM83 family oncogenes are broadly involved in human cancers: an integrative multi-omics approach},
author = {Snijders, Antoine M. and Lee, Sun-Young and Hang, Bo and Hao, Wenshan and Bissell, Mina J. and Mao, Jian-Hua},
abstractNote = {The development of novel targeted therapies for cancer treatment requires identification of reliable targets. FAM83 (‘family with sequence similarity 83’) family members A, B, and D were shown recently to have oncogenic potential. However, the overall oncogenic abilities of FAM83 family genes remain largely unknown. Here, we used a systematic and integrative genomics approach to investigate oncogenic properties of the entire FAM83 family members. We assessed transcriptional expression patterns of eight FAM83 family genes (FAM83A-H) across tumor types, the relationship between their expression and changes in DNA copy number, and the association with patient survival. By comparing the gene expression levels of FAM83 family members in cancers from 17 different tumor types with those in their corresponding normal tissues, we identified consistent upregulation of FAM83D and FAM83H across the majority of tumor types, which is largely driven by increased DNA copy number. Importantly, we found also that a higher expression level of a signature of FAM83 family members was associated with poor prognosis in a number of human cancers. In breast cancer, we found that alterations in FAM83 family genes correlated significantly with TP53 mutation, whereas significant, but inverse correlation was observed with PIK3CA and CDH1 (E-cadherin) mutations. We also identified that expression levels of 55 proteins were significantly associated with alterations in FAM83 family genes including a decrease in GATA3, ESR1, and PGR proteins in tumors with alterations in FAM83. Our results provide strong evidence for a critical role of FAM83 family genes in tumor development, with possible relevance for therapeutic target development.},
doi = {10.1002/1878-0261.12016},
journal = {Moletular Oncology},
number = 2,
volume = 11,
place = {United States},
year = {Mon Jan 09 00:00:00 EST 2017},
month = {Mon Jan 09 00:00:00 EST 2017}
}

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