Five subtypes of CMT (CMT1A/ PMP22 duplication, CMT1X/ GJB1 mutation, CMT2A/ mutationation, CMT1B/ MPZ mutation, and hereditary neuropathy with liability to pressure palsy/ PMP22 deletion) accounted for 89.2% of all genetically confirmed mutations.
High-risk groups for PDAC comprises individuals with a family history of pancreatic cancer, hereditary pancreatitis, new onset (<4 years), type 2 diabetes mellitus, obesity, Peutz Jeghers disorder, cystic fibrosis, familial cancer syndromes such as Lynch syndrome, adenomatous polyposis (APC mutation), and hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutations).
Mismatch repair is essential for retaining the fidelity of genetic information and defects in this pathway result in the deleterious accumulation of mutations and in hereditary diseases in humans.
Given our and other existing data on the tumour microenvironment (Dancey and Freidlin, 2003; Fukino et al, 2004), it may be postulated that the high frequencies of stromal EGFR mutations in sporadic and hereditary breast cancers could confound responsiveness to EGFR-TKI and may help explain interpatient variation.
See related research by Desrichard et al., http://breast-cancer-research.com/content/13/6/R119 We read with great interest the recent Breast Cancer Research paper by Desrichard and colleagues [ 1] reporting the association between CHEK2 mutations and non-BRCA hereditary breast cancer risk.
Some of these changes have been characterized to provide a clear contribution to the development and/or progression of the cancer and include overexpression of HER2/neu in about 20% of breast cancer [1], and hereditary mutations in BRCA1 or BRCA2 in approximately 5% of breast cancers [2].
Not surprisingly, DDR defects are associated with genomic instability and tumor development, and hereditary mutations leading to DDR impairment cause heightened cancer predisposition as well as various other age-related pathologies [reviewed in (1, 2)].
The mechanisms of amyloidogenesis in these cases are variable and include abnormal protein production, overproduction or decreased excretion of wild-type proteins and hereditary mutation.
Despite the difference in mutation frequencies between sporadic and hereditary breast cancers, it is obvious that sporadic and heritable breast cancers both have a similarly high frequency of EGFR mutations in tumour stroma, and that the majority of missense mutations lie in exon 20, in contrast to those in NSCLC.
