1. ¹Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, Edgbaston, Birmingham, UK
2. ²Department of Pathology, University of Cambridge, Cambridge, UK
3. ³Department of Pathology, Ninewells Hospital and Medical School, Dundee, UK
4. ⁴Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, UK

Correspondence: Dr FM Richards, Current address: DanioLabs Ltd., 7330, Cambridge Research Park, Waterbeach, Cambs CB5 9TN, UK. E-mail: fran.richards@daniolabs.com

⁵Current address: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Received 11 November 2004; Revised 19 July 2005; Accepted 25 July 2005; Published online 19 September 2005.

Abstract

The MSSE gene predisposes to multiple invasive but self-healing skin tumours (multiple self-healing epitheliomata). MSSE was previously mapped to chromosome 9q22–q31 and a shared haplotype in affected families suggested a founder mutation. We have refined the MSSE critical region (<1 cM, <1 Mb) between the zinc-finger gene ZNF169 and the Fanconi anaemia gene FANCC. By genetic mapping we have excluded ZNF169 and FANCC as well as PTCH (PATCHED) and TGFBR1 (transforming growth factor beta receptor type-1) genes. The CDC14B cell cycle phosphatase gene also lies in the region but screening of the complete coding region revealed no mutation in MSSE patients. Somatic cell hybrids created by haploid conversion of an MSSE patient's cells enabled screening of the MSSE chromosome 9 and showed no CDC14B deletion or mutation that abrogates CDC14B mRNA expression. Thus, CDC14B is unlikely to be the MSSE gene. We also report the first molecular analysis of MSSE tumours showing loss of heterozygosity of the MSSE region, with loss of the normal allele, providing the first evidence that MSSE is a tumour suppressor gene.