Germ line mutations

BRCAl and BRCA2 are frequently mutated in a variety of human cancers. Breast cancer is the most common malignancy in women. A total of more than a million women will be diagnosed with breast cancer worldwide with more than 400,000 deaths annually. The germ line mutations of BRCAl/2 are associated with hereditary breast cancer which account for 5-7% of all breast cancer cases (12, 13). Ovarian cancer is the leading cause of death from gynecological cancer with more than 140,000 deaths annually worldwide. The germ line and somatic BRCAl/2 mutations have been reported to occur in approximately 10% of ovarian cancer patients (14, 15). BRCAl/2 mutations have also been shown to occur frequently in Ashkenazi Jewish families with pancreatic cancer (16). 

Aaron/ C.S. Molecular dosimetry of chemical mutagens selection of appropriate target molecules for determining molecular dose to the germ line. Mutat. Res. 38 303-310, 1976. 

In familial prion diseases germ line mutations in the prion protein gene leads to PrP " deposition in the brain and nervous system. Prion agent has not been found in peripheral tissues in the limited number of familial prion disease cases that have been examined. 

Gerstmann-Straussler-Sclieinker (GSS) syndrome is a prion disease linked to germ line mutations or insertions in the human prion protein gene resulting in a neurodegenerative brain disorder. 

E200K-129M 3-5% Germ line mutation in PRNP... 

Gerstmann-Straussler-Scheinker Acquired (-l ) 72 families Germ line mutations/ insertions in PRNP... 

No information was identified on parental exposures affecting children in areas of parental germ cells or germ line mutations. The topic of exposure pathways for mercury via nursing or pregnant women who have been exposed is of main concern and has been addressed earlier in this section. 

Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002 346 1459-66. 

Nagase H, Miyoshi Y, Horii A, Aoki T, Agawa M, Utsunomiya J, et al. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Res 1992 52 4055-7. 

Essential for assessment of the impact of pollutants at population level is the distinction that is made between somatic and germ-line mutations. Mutations in somatic cells may (among other effects) induce neoplasia, but because they do not occur in cells that give rise to gametes the mutation will not be passed on to the next generations. 

The mtDNA has a very high mutation rate, some 10-17 times higher than nDNA, which affects both germ line and somatic tissue mtDNAs. Germ line mutations result in maternally transmitted diseases or predispose individuals to late-onset degenerative... 

Each oncogene must be activated by a mutation. Most are activated by one or more somatic mutations. Germ line mutations that activate oncogenes lead to familial cancers. 

Germ-line mutations in an oncogene, with somatic mutations that suppress the oncogene... 

Germ-line mutations in a tumor suppressor gene, with neoplasia from chemical exposure... 

The answer is b. (Murray, pp 787-811. Scriver, pp 521-552. Sack, pp 85—96. Wilson, pp 187-224.) Genetic predisposition to cancer is best understood by the Knudsen hypothesis, where two independent mutations or hits are required to produce neoplasia of a somatic tissue. In many hereditary cancers, the first hit is a germ-line mutation that is transmitted in families. Individuals who inherit this mutation are much more likely to... 

Rubin SC, Benjamin I, Behbakht K. Clinical and pathological features in women with germ-line mutations of BRCAl. N Engl J Med 1996 335 1413-1416. 

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