Publication Date:
2010-09-10
Description:
Ovarian clear cell carcinoma (OCCC) is an aggressive human cancer that is generally resistant to therapy. To explore the genetic origin of OCCC, we determined the exomic sequences of eight tumors after immunoaffinity purification of cancer cells. Through comparative analyses of normal cells from the same patients, we identified four genes that were mutated in at least two tumors. PIK3CA, which encodes a subunit of phosphatidylinositol-3 kinase, and KRAS, which encodes a well-known oncoprotein, had previously been implicated in OCCC. The other two mutated genes were previously unknown to be involved in OCCC: PPP2R1A encodes a regulatory subunit of serine/threonine phosphatase 2, and ARID1A encodes adenine-thymine (AT)-rich interactive domain-containing protein 1A, which participates in chromatin remodeling. The nature and pattern of the mutations suggest that PPP2R1A functions as an oncogene and ARID1A as a tumor-suppressor gene. In a total of 42 OCCCs, 7% had mutations in PPP2R1A and 57% had mutations in ARID1A. These results suggest that aberrant chromatin remodeling contributes to the pathogenesis of OCCC.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076894/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076894/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Sian -- Wang, Tian-Li -- Shih, Ie-Ming -- Mao, Tsui-Lien -- Nakayama, Kentaro -- Roden, Richard -- Glas, Ruth -- Slamon, Dennis -- Diaz, Luis A Jr -- Vogelstein, Bert -- Kinzler, Kenneth W -- Velculescu, Victor E -- Papadopoulos, Nickolas -- CA103937/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA122581/CA/NCI NIH HHS/ -- CA129080/CA/NCI NIH HHS/ -- CA57345/CA/NCI NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-05/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- R37 CA057345-20/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Oct 8;330(6001):228-31. doi: 10.1126/science.1196333. Epub 2010 Sep 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20826764" target="_blank"〉PubMed〈/a〉
Keywords:
Adenocarcinoma, Clear Cell/*genetics
;
Adult
;
Cell Line, Tumor
;
Chromatin Assembly and Disassembly/*genetics
;
Female
;
*Genes, Tumor Suppressor
;
Genes, ras
;
Humans
;
Middle Aged
;
*Mutation
;
Nuclear Proteins/chemistry/*genetics/metabolism
;
Oncogenes
;
Ovarian Neoplasms/*genetics
;
Phosphatidylinositol 3-Kinases/genetics
;
Protein Phosphatase 2/*genetics
;
Sequence Analysis, DNA
;
Transcription Factors/chemistry/*genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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