A continuum model for tumour suppression.

Nature 2011 Aug 10;476(7359):163-9. Epub 2011 Aug 10.

Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts 02115, USA.

This year, 2011, marks the forty-year anniversary of the statistical analysis of retinoblastoma that provided the first evidence that tumorigenesis can be initiated by as few as two mutations. This work provided the foundation for the two-hit hypothesis that explained the role of recessive tumour suppressor genes (TSGs) in dominantly inherited cancer susceptibility syndromes. However, four decades later, it is now known that even partial inactivation of tumour suppressors can critically contribute to tumorigenesis. Here we analyse this evidence and propose a continuum model of TSG function to explain the full range of TSG mutations found in cancer.

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature10275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206311PMC
August 2011
3 Reads

Publication Analysis

Top Keywords

continuum model
8
role recessive
4
explained role
4
recessive tumour
4
analyse evidence
4
suppressor genes
4
evidence propose
4
tumour suppressor
4
propose continuum
4
work provided
4
mutations work
4
provided foundation
4
foundation two-hit
4
tumorigenesis analyse
4
two-hit hypothesis
4
hypothesis explained
4
genes tsgs
4
syndromes decades
4
suppressors critically
4
decades partial
4

References

(Supplied by CrossRef)

PC Nowell et al.
J. Natl Cancer Inst. 1960

JD Rowley et al.
Nature 1973

JD Rowley et al.
Lancet 1977

N Heisterkamp et al.
Nature 1983

PP Pandolfi et al.
Oncogene 1991

D Stehelin et al.
Nature 1976

H Oppermann et al.
Proc. Natl Acad. Sci. USA 1979

H Harris et al.
Cancer Res. 1988

AG Knudson Jr et al.
Proc. Natl Acad. Sci. USA 1971

WH Lee et al.
Science 1987

YK Fung et al.
Science 1987

Similar Publications