Loss of expression of chromosome 16q genes DPEP1 and CTCF in lobular carcinoma in situ of the breast.
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.
Green
Andrew R
AR
Division of Pathology, School of Molecular Medical Sciences, University of Nottingham and Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham, UK NG7 2UH. andrew.green@nottingham.ac.uk
Krivinskas
Sophie
S
Young
Peter
P
Rakha
Emad A
EA
Paish
E Claire
EC
Powe
Desmond G
DG
Ellis
Ian O
IO
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D000076246:CCCTC-Binding Factor; D002278:Carcinoma in Situ / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm; D012337:RNA, Ribosomal, 18S; D012097:Repressor Proteins