During the past several decades, genetic testing for germline and somatic mutations has been incorporated into routine clinical practice for many different cancer types. Germline mutations, contained within the heritable genome, and somatic mutations, acquired de novo by cancer cells, have historically been considered as separate entities. Until recently, each had unique clinical applications and implications for patient care.
A Genomic Disease
For decades, the prevailing paradigm in oncology research has been that cancer is driven predominantly by the accumulation of mutations in the genetic material as a result of DNA-damaging chemical or environmental assaults on the cell. Anywhere from 2 to 8, potentially as many as 20 mutations, are required for the development of a cancer.3,4
Figure. Origins of Mutations in Cancer5
In some genes, germline mutations have been linked to the development of certain types of cancers and form the genetic basis of several wellknown hereditary cancer syndromes (Table 1).6
Table. Hereditary Cancer Syndromes6
The best characterized of these likely are hereditary breast and ovarian cancers (HBOCs), caused by germline mutations in the breast cancer susceptibility genes BRCA1
. It is estimated that approximately 1% of the general population carries germline BRCA1/2
mutations. Their presence increases the risk of developing ovarian cancer from about 1.3% to 39% (BRCA1) and 11% to 17% (BRCA2
); for breast cancer, the increased risk ranges from 12% to 55% or 65% (BRCA1
) and up to 45% (BRCA2
mutations have also been implicated in several other tumor types, including prostate and pancreatic cancer.
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