DNA methylation of RASSF1A, HIN-1, RAR-β, cyclin D2 and twist in in situ and invasive lobular breast carcinoma

Mary Jo Fackler, Megan McVeigh, Ella Evron, Elizabeth Garrett, Jyoti Mehrotra, Kornelia Polyak, Saraswati Sukumar, Pedram Argani

Research output: Contribution to journalArticle

Abstract

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-β, 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, RARβ, 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 hypermethylated 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.

Original languageEnglish (US)
Pages (from-to)970-975
Number of pages6
JournalInternational Journal of Cancer
Volume107
Issue number6
DOIs
StatePublished - Dec 20 2003

Fingerprint

Cyclin D2
Lobular Carcinoma
DNA Methylation
Methylation
Breast Neoplasms
Genes
Gene Silencing
Neoplasms
Ductal Carcinoma
Mammaplasty
Neoplasm Genes
Epigenomics
Polymerase Chain Reaction
DNA

Keywords

  • Breast cancer
  • DCIS
  • Ductal
  • LCIS
  • Lobular
  • Methylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

DNA methylation of RASSF1A, HIN-1, RAR-β, cyclin D2 and twist in in situ and invasive lobular breast carcinoma. / Fackler, Mary Jo; McVeigh, Megan; Evron, Ella; Garrett, Elizabeth; Mehrotra, Jyoti; Polyak, Kornelia; Sukumar, Saraswati; Argani, Pedram.

In: International Journal of Cancer, Vol. 107, No. 6, 20.12.2003, p. 970-975.

Research output: Contribution to journalArticle

Fackler, Mary Jo ; McVeigh, Megan ; Evron, Ella ; Garrett, Elizabeth ; Mehrotra, Jyoti ; Polyak, Kornelia ; Sukumar, Saraswati ; Argani, Pedram. / DNA methylation of RASSF1A, HIN-1, RAR-β, cyclin D2 and twist in in situ and invasive lobular breast carcinoma. In: International Journal of Cancer. 2003 ; Vol. 107, No. 6. pp. 970-975.
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abstract = "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-β, 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, RARβ, 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 hypermethylated 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.",
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AU - Garrett, Elizabeth

AU - Mehrotra, Jyoti

AU - Polyak, Kornelia

AU - Sukumar, Saraswati

AU - Argani, Pedram

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AB - 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-β, 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, RARβ, 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 hypermethylated 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.

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