title: The patched/hedgehog/smoothened signalling pathway in human breast cancer: no evidence for H133Y SHH, PTCH and SMO mutations.
abstract: The patched/hedgehog/smoothened signalling pathway has been implicated in the development of sporadic tumours associated with the naevoid basal cell carcinoma (Gorlin) syndrome (NBCCS). Mutations in sporadic basal cell carcinomas (BCCs) of the skin and medulloblastomas have been found in genes encoding all three proteins of the pathway. A substantial proportion of breast carcinomas has recently been suggested to contain missense mutations in the human patched (PTCH) and sonic hedgehog (SHH) homologues. However, an independent study showed that the implicated mutation in SHH (H133Y) was absent in a large number of BCCs, medulloblastomas, breast, ovary and colorectal tumours. We searched for the H133Y SHH mutation in 84 primary breast carcinomas, but did not detect this change in any sample. In addition, a subset of 45 primary breast tumours was analysed for mutations in the PTCH coding region and 48 samples in previously implicated exons of human smoothened, but no mutations were found. Although our results do not exclude the presence of clonal alterations of these genes in a small proportion of breast carcinomas, these data do not support the existence of frequent mutations in genes encoding major protein partners of this signalling pathway. The absence of nucleotide changes in PTCH may point to another linked gene in the chromosome region 9q22-q23, previously suggested to contain a breast cancer susceptibility gene.
authors.affiliation: Karolinska Institute, Department of Biosciences at Novum, Huddinge, Sweden. lgor.vorechovsky@cbt.ki.se
authors.forename: I
authors.initials: I
authors.lastname: Vorechovský
authors.forename: K P
authors.initials: KP
authors.lastname: Benediktsson
authors.forename: R
authors.initials: R
authors.lastname: Toftgård
mesh_terms: D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002450:Cell Communication; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D053823:Hedgehog Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators
chemical_list: D004273:DNA, Neoplasm; D053823:Hedgehog Proteins; D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators