A NOVEL HUMAN WNT GENE, WNT10B, MAPS TO 12Q13 AND IS EXPRESSED IN HUMAN BREAST CARCINOMAS

Several members of the Wnt gene family have been shown to cause mammar y tumors in mouse. Using degenerate primer polymerase chain reaction ( PCR) on human genomic DNA, and specific PCR of cDNA libraries, we have isolated a WNT gene which has not previously been described in human. The gene is the human homologue of mouse Wnt10b, recently shown to be one of the oncogenes cooperating with FGF3 in the development of mous e mammary tumour virus (MMTV) induced mouse mammary carcinomas. The hu man WNT10B sequence was 88% and 95% identical to the murine gene at nu cleotide and amino acid levels, respectively, YAC FISH mapping localis es the gene to 12q13, a chromosomal region frequently rearranged in hu man tumours and also containing the WNT1 gene. In normal and benign pr oliferations of human breast tissue, WNT10B expression was not detecte d by ribonuclease protection assays but was found at low levels in RT- PCR experiments. In contrast, using both methods, WNT10B expression wa s found to be elevated in 3 of 50 primary breast carcinomas. Southern blot analysis of the carcinoma expressing the highest levels of WNT10B showed no amplification or rearrangement of the gene. The WNT10B gene was also expressed in some cancer and non cancerous breast cell lines . These findings suggest that the WNT10B gene may be involved in human breast cancer, and show that there is differential expression of the WNT10B gene in benign and malignant disease.