RGD Reference Report - DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets.

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DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets.
Authors:	Wu, Q Lothe, RA Ahlquist, T Silins, I Trope, CG Micci, F Nesland, JM Suo, Z Lind, GE
Citation:	Wu Q, etal., Mol Cancer. 2007 Jul 10;6:45.
RGD ID:	2298986
Pubmed:	PMID:17623056 (View Abstract at PubMed)
PMCID:	PMC1964763 (View Article at PubMed Central)
DOI:	DOI:10.1186/1476-4598-6-45 (Journal Full-text)
BACKGROUND: The epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52) and their in vitro models (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3) by methylation-specific polymerase chain reaction (MSP). Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features. RESULTS: Eight out of the 13 genes were hypermethylated among the ovarian carcinomas, and altogether 40 of 52 tumours were methylated in one or more genes. Promoter hypermethylation of HOXA9, RASSF1A, APC, CDH13, HOXB5, SCGB3A1 (HIN-1), CRABP1, and MLH1 was found in 51% (26/51), 49% (23/47), 24% (12/51), 20% (10/51), 12% (6/52), 10% (5/52), 4% (2/48), and 2% (1/51) of the carcinomas, respectively, whereas ADAMTS1, MGMT, NR3C1, p14ARF, and p16INK4a were unmethylated in all samples. The methylation frequencies of HOXA9 and SCGB3A1 were higher among relatively early-stage carcinomas (FIGO I-II) than among carcinomas of later stages (FIGO III-IV; P = 0.002, P = 0.020, respectively). The majority of the early-stage carcinomas were of the endometrioid histotype. Additionally, HOXA9 hypermethylation was more common in tumours from patients older than 60 years of age (15/21) than among those of younger age (11/30; P = 0.023). Finally, there was a significant difference in HOXA9 methylation frequency among the histological types (P = 0.007). CONCLUSION: DNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis and HOXA9, HOXB5, SCGB3A1, and CRABP1 are identified as novel hypermethylated target genes in this tumour type.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Ovarian Neoplasms		ISO	CDH13 (Homo sapiens)	2298986	DNA:hypermethylation:promoter	RGD

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Genes (Mus musculus)

Cdh13 (cadherin 13)

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Gene	CDH13	cadherin 13	Homo sapiens
Gene	Cdh13	cadherin 13	Rattus norvegicus

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DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets.