DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma.
Little is known about epigenetic silencing of genes by promoter hypermethylation in lobular breast cancers. The promoter methylation status of 5 cancer-related genes (RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist) was evaluated in 2 types of lobular cancers, in situ (LCIS) and invasive lobular carcinomas (ILC) (n = 32), and compared to ductal in situ (DCIS) and invasive (IDC) breast cancers (n = 71). By using methylation-specific PCR (MSP), 100% of ILC and 69% of LCIS cases were found to have 1 or more hypermethylated genes among the panel of 5 genes (compared to 100% IDC and 95% of DCIS). Two or more hypermethylated genes were detected per tumor in 79% of invasive and 61% of in situ lobular carcinomas compared to 81% of IDC and 77% of DCIS. By contrast, DNA from nearly all normal reduction mammoplasty tissues (n = 8) was unmethylated for the 5 genes. The methylation profiles of lobular vs. ductal carcinomas with respect to RASSF1A, Cyclin D2, RARbeta, and Hin-1 genes were similar, suggesting that gene silencing by promoter hypermethylation is likely to be important in both groups of diseases. Distinctly different, Twist was hyper- methylated less often in ILC (16%, 3/19 cases) than in IDC (56%, 15/27 cases) (p = 0.01). These results suggest that these 2 types of tumors share many common methylation patterns and some molecular differences. Additional studies might lend further understanding into the etiology and clinical behavior of this tumor type.
Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N. Broadway, Baltimore, MD 21231-2410, USA.
Mary Jo
MJ
Fackler
Megan
M
McVeigh
Ella
E
Evron
Elizabeth
E
Garrett
Jyoti
J
Mehrotra
Kornelia
K
Polyak
Saraswati
S
Sukumar
Pedram
P
Argani
D000328:Adult; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000473:pathology; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D005810:Multigene Family; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D051879:Twist-Related Protein 1
C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D016207:Cytokines; D017931:DNA Primers; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; C434732:SCGB3A1 protein, human; C103173:TWIST1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051879:Twist-Related Protein 1; C082925:retinoic acid receptor beta