According to Knudson's two-hit hypothesis, the difference between hereditary and sporadic retinoblastoma is best explained by which statement?

• A Hereditary cases have one hit already present in the germline, so only one somatic mutation is needed ✓
• B Hereditary cases require two somatic mutations, while sporadic cases require one germline and one somatic mutation
• C Sporadic cases are caused by oncogenic viruses, while hereditary cases are caused by chemical carcinogens
• D Hereditary cases involve activation of an oncogene, while sporadic cases involve loss of a tumor suppressor gene

Explanation

Knudson's two-hit hypothesis states that retinoblastoma requires biallelic inactivation of the RB1 tumor suppressor gene. In hereditary cases, one mutated allele is inherited in the germline, so only one somatic mutation is needed. In sporadic cases, both hits must occur somatically in the same cell, making it less likely and later in life. This is the classic model for tumor suppressor gene inactivation.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.