The patched/hedgehog/smoothened signalling pathway in human breast cancer:No evidence for H133YSHH, PTCH and SMO mutations

The patched/hedgehog/smoothened signalling pathway has been implicated in t he development of sporadic tumours associated with the naevoid basal cell c arcinoma (Gorlin) syndrome (NBCCS). Mutations in sporadic basal cell carcin omas (BCCs) of the skin and medulloblastomas have been found in genes encod ing all three proteins of the pathway. A substantial proportion of breast c arcinomas has recently been suggested to contain missense mutations in the human patched (PTCH) and sonic hedgehog (SHH) homologues. However, an indep endent study showed that the implicated mutation in SHH (H133Y) was absent in a large number of BCCs, medulloblastomas, breast, ovary and colorectal t umours. We searched for the H133Y SHH mutation in 84 primary breast carcino mas, 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 re gion 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 carcin omas, these data do not support the existence of frequent mutations in gene s encoding major protein partners of this signalling pathway. The absence o f nucleotide changes in PTCH may point to another linked gene in the chromo some region 9q22-q23, previously suggested to contain a breast cancer susce ptibility gene. (C) 1999 Elsevier Science Ltd. All rights reserved.