Table 1 |.

Alterations of the RB gene in common human cancer types

Tumour type	Frequency of RB inactivation (genetic or epigenetic)	Presumed consequence of RB inactivation	Refs
Lung cancer	Germline RB mutations predispose to small cell lung carcinoma (SCLC), and RB is inactivated in >90% of sporadic SCLC cases. In contrast, RB is mutated in only 15–30% of non-SCLC cases.	SCLC initiation; progression to invasive forms of non-SCLC	182–184
Melanoma	RB inactivation is rare in sporadic cases, but inherited mutation predisposes to melanoma	Initiating event in familial cases	185,186
Prostate cancer	~20%	Progression to invasive carcinoma‡	187–189
Breast cancer	~20%	Progression	190,191
Bladder cancer	20–50%	Progression to invasive tumours	184,192–194
Leukaemia	Reduced levels of expression are frequent, but mutations in RB are rare in leukaemias, except in 20% of chronic myeloid leukaemia (CML) cases	Progression (CML blast crisis)	195–197
Brain cancer	Rb-mutant mice develop pituitary tumours, but RB mutations are rare in human cases. 15–30% of advanced gliomas have RB mutations	Progression	198–201
Oesophageal cancer	RB deletion are found in 15–50% of adenocarcinomas or squamous cell carcinomas	Early progression	202,203
Liver cancer	Mutations in RB are found in 15–30% of the advanced hepatocellular carcinomas§	Progression	137,204–206

^*Inactivation of Rb in the lung epithelial of mice is sufficient to initiate neuroendocrine hyperplasia²¹⁶ but the additional loss of Trp53 is required for SCLC development²⁴.

^‡Rb deletion in a mouse model is sufficient to initiate prostate cancer^217,218.

^§Overexpression of Gankyrin in liver tumours might functionally inactivate RB, potentially bypassing the need to mutate RB in many cases²¹⁹, similar to the expression of E7 by HPV in cervical cancer. Note that cells from common cancers such as colorectal carcinoma²⁰⁷, pancreatic carcinoma²⁰⁸, renal cell carcinoma²⁰⁹, endometrial carcinoma, ovarian carcinoma²¹⁰, non-Hodgkin lymphoma^211,212, myeloma²¹³, thyroid carcinoma²¹⁴, HPV-negative head and neck carcinoma²² and gastric carcinoma²¹⁵ only rarely carry mutations in RB. However, in many cases, RB is hyperphosphorylated or shows decreased levels in these tumours, and mutations in other members of the RB pathway are usually present.