BACKGROUND: Loss of the chromosomal material at 16q is the most frequent genetic event in invasive and in situ (LCIS) lobular carcinoma of the breast. However, the smallest region of overlap at 16q is not restricted to just the CDH1 locus harbouring E-cadherin, suggesting that neighbouring genes might be involved in the development and progression of these tumours. Potential novel tumour suppressor genes (TSG) at 16q include CCCTC-binding factor (CTCF), Decreased Expression in Renal and Prostate Cancer (DERPC) and Dipeptidase 1 (DPEP1). The aim of this study is to assess the expression of these genes in LCIS and compare them with normal breast, using CDH1 as a control, in order to evaluate their role as TSGs. METHODS: Cells from LCIS cases and normal breast lobules were microdissected and expression of target genes were quantified using real-time PCR. In addition, immunohistochemistry (IHC) for E-cadherin and CTCF was performed on paraffin processed LCIS (n=49) and normal breast cases. RESULTS: All LCIS showed negative expression of E-cadherin. Similar to CDH1, CTCF and DPEP1 gene expression was significantly lower in LCIS cases compared with normal cases (P<0.05). CTCF IHC expression showed significant reduction in LCIS compared to normal parenchymal cells. However, there was no difference in expression of DERPC between LCIS and normal breast tissue. CONCLUSIONS: In addition to CDH1, loss of CTCF and DPEP1 gene expression suggest they are possible TSG in breast cancer and may, similar to CDH1, be potentially utilised as markers of predisposition of women diagnosed with LCIS.
BACKGROUND: Loss of the chromosomal material at 16q is the most frequent genetic event in invasive and in situ (LCIS) lobular carcinoma of the breast. However, the smallest region of overlap at 16q is not restricted to just the CDH1 locus harbouring E-cadherin, suggesting that neighbouring genes might be involved in the development and progression of these tumours. Potential novel tumour suppressor genes (TSG) at 16q include CCCTC-binding factor (CTCF), Decreased Expression in Renal and Prostate Cancer (DERPC) and Dipeptidase 1 (DPEP1). The aim of this study is to assess the expression of these genes in LCIS and compare them with normal breast, using CDH1 as a control, in order to evaluate their role as TSGs. METHODS: Cells from LCIS cases and normal breast lobules were microdissected and expression of target genes were quantified using real-time PCR. In addition, immunohistochemistry (IHC) for E-cadherin and CTCF was performed on paraffin processed LCIS (n=49) and normal breast cases. RESULTS: All LCIS showed negative expression of E-cadherin. Similar to CDH1, CTCF and DPEP1 gene expression was significantly lower in LCIS cases compared with normal cases (P<0.05). CTCF IHC expression showed significant reduction in LCIS compared to normal parenchymal cells. However, there was no difference in expression of DERPC between LCIS and normal breast tissue. CONCLUSIONS: In addition to CDH1, loss of CTCF and DPEP1 gene expression suggest they are possible TSG in breast cancer and may, similar to CDH1, be potentially utilised as markers of predisposition of women diagnosed with LCIS.
Authors: Ming Tang; Bo Chen; Tong Lin; Zhaozhong Li; Carolina Pardo; Christine Pampo; Jing Chen; Ching-Ling Lien; Lizi Wu; Lingbao Ai; Heiman Wang; Kai Yao; S Paul Oh; Edward Seto; Lois E H Smith; Dietmar W Siemann; Michael P Kladde; Constance L Cepko; Jianrong Lu Journal: Proc Natl Acad Sci U S A Date: 2011-09-06 Impact factor: 11.205
Authors: Phuongmai Nguyen; Hengmi Cui; Kheem S Bisht; Lunching Sun; Krish Patel; Richard S Lee; Hiroyuki Kugoh; Mitsuo Oshimura; Andrew P Feinberg; David Gius Journal: Cancer Res Date: 2008-07-15 Impact factor: 12.701
Authors: Geng Zhang; Aaron Schetter; Peijun He; Naotake Funamizu; Jochen Gaedcke; B Michael Ghadimi; Thomas Ried; Raffit Hassan; Harris G Yfantis; Dong H Lee; Curtis Lacy; Anirban Maitra; Nader Hanna; H Richard Alexander; S Perwez Hussain Journal: PLoS One Date: 2012-02-20 Impact factor: 3.240