Retinoblastoma and the genetic theory of cancer: an old paradigm trying to survive to the evidence.
Retinoblastoma (Rb) is considered to represent the prototype of cancer linked to the sequential loss or inactivation of both alleles of a so-called "tumor suppressor gene", the Rb1 gene. The pathogenetic mechanism behind this tumor was first hypothesized by Knudson in 1971 and further confirmed by others who identified the Rb1 gene whose loss or inactivation was claimed to be responsible for the disease. However, after about four decades of continuous research in the field of molecular biology, the evidence behind the role of the Rb1 gene in Rb appears to be seriously flawed in the light of epidemiological, biological, and clinical evidences. This editorial summarizes the inconsistencies on this subject. Nevertheless, the molecular biology establishment still adheres to the biased view of the genetic origin of Rb and other cancers, and hardly any alternative explanations are taken into account.
Mastrangelo
Domenico
D
Department of Biomedical Sciences, University of Siena, 53100 Siena, Italy.
Hadjistilianou
Theodora
T
De Francesco
Sonia
S
Loré
Cosimo
C
Proc Natl Acad Sci U S A. 1975 Dec;72(12):5116-20
1061095
Cancer. 1977 Apr;39(4 Suppl):1882-6
851956
Cancer Lett. 2007 Sep 18;255(1):12-25
17383090
Cancer. 1975 Mar;35(3 suppl):1022-6
163140
Cancer. 1986 Aug 1;58(3):663-71
3524791
Clin Ter. 2000 Nov-Dec;151(6):433-8
11211478
Eur J Cancer. 2006 Jul;42(11):1520-9
16781866
Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3
5279523
N Engl J Med. 1979 Sep 13;301(11):606-7
470983
Cell Death Differ. 2004 Jan;11(1):11-2
14685167
Genes Chromosomes Cancer. 2003 Dec;38(4):288-91
14566844
Best Pract Res Clin Haematol. 2007 Sep;20(3):439-53
17707832
Am J Med. 1980 Jul;69(1):1-3
7386496
Annu Rev Genomics Hum Genet. 2005;6:1-14
16124851
JAMA. 1979 Jan 19;241(3):279
758536
J Cancer Res Clin Oncol. 1996;122(3):135-40
8601560
Proc Natl Acad Sci U S A. 1978 May;75(5):2453-7
276883
Ophthalmic Paediatr Genet. 1989 Jun;10(2):129-50
2674826
Ai Zheng. 2002 Jan;21(1):1-10
12500388
Pathologe. 1998 Jan;19(1):63-8
9541944
Retina. 2004 Dec;24(6):849-62
15579981
Med Sci Monit. 2008 Dec;14(12):RA231-40
19043380
J Natl Cancer Inst Monogr. 1995;(17):5-7
8573454
Genetics. 1975 Jun;79 Suppl:305-16
238902
Curr Opin Ophthalmol. 2006 Jun;17(3):228-34
16794434
Curr Opin Ophthalmol. 2008 Nov;19(6):526-34
18854698
Histol Histopathol. 2003 Jul;18(3):897-909
12792902
Cancer Res. 1985 Apr;45(4):1437-43
2983882
Cancer. 1989 May 15;63(10):1888-91
2702563
Int J Cancer. 2007 Dec 1;121(11):2501-5
17657745
Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10914-21
7902574
Am J Pathol. 1974 Oct;77(1):77-84
4447124
Eur J Cancer. 2007 Jul;43(10):1596-603
17543516
Int J Cancer. 2003 Feb 20;103(5):616-23
12494468
Am J Med Genet. 2002 Jul 22;111(1):96-102
12124744
Hum Mutat. 2009 May;30(5):842-51
19280657
Bull Cancer. 2002 Feb;89(2):166-73
11888856