Question

Answer in a few sentences: How can a germline mutation predispose someone to particular types of cancer? How is this similar/different to development of cancer in someone without any such germline mutation?

Answer 1

Individuals with inherited mutation in tumor suppressor genes have a hereditary predisposition for certain cancers. Such individuals inherit a germline mutation in one allele of the gene from either of his parents. Somatic mutation of the second allele initiates tumor development. Such cancers constitute about 10% of human cancers.

An example is Retinoblastoma. Retinoblastoma occurs when both copies of the RB gene are inactivated by various types of lesions. This gene is located in the band q14 of human chromosome 13. In the inherited state of the disease, one parental chromosome carries a loss of function mutataion in the RB gene. A somatic mutataion in retinal cells that causes loss of the other copyof the RB gene causes a tumor.

A normal individual has two wild type copies of the RB gene. In such individuals loss of both the RB alleles in the same retinal cell is required for transformation.