Expression analysis of candidate breast tumour suppressor genes on chromosome 16q.
BACKGROUND
Chromosome arm 16q is the second most frequent target of loss of heterozygosity in breast cancer and is, therefore, a candidate to contain one or more classic tumour suppressor genes (TSGs). E-cadherin at 16q22 was identified as a TSG in lobular breast cancer, but TSGs in ductal breast cancer remain elusive. Several genes have been suggested as potential candidates (e.g. CBFA2T3, CTCF and WWOX) but no inactivating mutations could be identified in these genes and they thus fail to fit the classic two-hit model for a TSG. With the completion of the human transcriptome, new candidate genes can be distinguished. Besides mutational inactivation, a TSG could, at least in a subset of the tumours, be transcriptionally suppressed or even inactivated. Studying candidate genes for expression and somatic mutations could thus identify the TSGs.


METHODS
Possible candidates CBFA2T3, TERF2 and TERF2IP, FBXL8 and LRRC29 and FANCA were studied for insertion and deletion mutations and for expression differences using quantitative RT-PCR in a panel of tumour cell lines and primary tumours with and without loss of 16q.


RESULTS
None of the genes showed mutations or obvious expression differences. FANCA expression increased with tumour grade.


CONCLUSIONS
Apparently, the underlying genetics at chromosome 16q are complex or the TSGs remain to be identified. Multiple mechanisms, such as mutations, promoter hypermethylation or haploinsufficiency, might lead to the inactivation of a TSG.
van Wezel
Tom
T
Department of Pathology, Leiden University Medical Center, Albiniusdreef 2, 2333ZA Leiden, The Netherlands. t.van_wezel@lumc.nl
Lombaerts
Marcel
M
van Roon
Eddy H
EH
Philippo
Katja
K
Baelde
Hans J
HJ
Szuhai
Karoly
K
Cornelisse
Cees J
CJ
Cleton-Jansen
Anne-Marie
AM
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002885:Chromosomes, Human, Pair 16; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D020133:Reverse Transcriptase Polymerase Chain Reaction