Question 1

What does RB1 do?

Accepted Answer

RB1 encodes pRb, which controls the G1/S restriction point by binding and sequestering E2F transcription factors. Hypophosphorylated pRb actively represses E2F target genes needed for S-phase entry. CDK4/6-cyclin D phosphorylation liberates E2F and commits the cell to division — a point of no return.

Question 2

What cancers are caused by RB1 mutations?

Accepted Answer

Biallelic RB1 loss causes retinoblastoma — the first cancer explained by Knudson's two-hit hypothesis. Somatic RB1 inactivation is near-universal in small cell lung cancer (~90%), common in bladder cancer and osteosarcoma, and occurs in approximately 20% of breast and prostate cancers.

Question 3

Does RB1 status predict response to CDK4/6 inhibitors?

Accepted Answer

Yes — CDK4/6 inhibitors work by keeping pRb in its active hypophosphorylated state. Tumours with RB1 deletion or mutation are intrinsically resistant to CDK4/6 inhibitors because there is no pRb to protect. RB1 status is therefore a critical predictive biomarker for palbociclib, ribociclib, and abemaciclib.

RB1 Gene Function

Overview

More Tumor Suppressor Genes