RB1 and cancer: Despite the notion that cancer does cluster in families, a concept spearheaded by the late Henry Lynch in the mid-1970s (Lynch, 1974), the application of genetic testing to validate the clinical impression of an inherited predisposition to cancer was initially limited to a few high-risk, high-penetrance genes that underlie rare monogenic disorders (e.g., Rb, APC, VHL, and RET).