Our study inthe New England Journal of Medicine lays the groundwork to understand the spectrum of cancers and age-specific cancer risks associated with germline mutations
in predisposition genes and how best to monitor at-risk patients and families," said co-author Kim Nichols, M.
TP53 germline mutations
are found in 70% of LFS patients who undergo genetic testing.
PDGFRA germline mutation
in a family with multiple cases of gastrointestinal stromal tumor.
This syndrome results from germline mutation
of the NF1 gene, which encodes for a GTPase-activating protein, neurofibromin.
This fact led to failure of the GS-FLX to identify a germline mutation
in MSH2 known to cause Lynch syndrome (IVS5 + 3A>T, samples 2 and 6) (Table 4).
2) Colorectal cancer associated with a germline mutation
in a MMR gene accounts for about 3% of all colorectal cancers and is by far the most common heritable cause of colon cancer.
Hereditary breast and ovarian cancer syndrome is an autosomal, dominantly inherited disease characterized by early development of breast and ovarian cancer and germline mutation
of BRCA2 and BRCA1.
The median age at diagnosis was 54 years in men and 70 years in women in a group of 70 Finnish families at risk for hereditary nonpolyposis colorectal cancer (HNPCC) that comprised 88 probands and 373 individuals who tested positive for a germline mutation
in MLH1 or MSH2 (Gastroenterology 2005;129:415-21).
A small percentage of CRCs that arise via the MSI pathway are inherited as the result of a germline mutation
in one of the mismatch repair (MMR) genes (Lynch syndrome/hereditary nonpolyposis colon cancer [HNPCC]; about 2% to 5% of all cases of CRCs).
Coexisting somatic promoter hypermethylation and pathogenic MLH1 germline mutation
in Lynch syndrome.
12) Most patients with LFS carry a germline mutation
in one TP53 allele; in many cases, somatic mutation of the other allele is present in the tumor.
5) Almost all patients have a detectable germline mutation
in the VHL tumor-suppressor gene located on chromosome short arm 3 (3p25-3p26).