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Two genetic hits (more or less) to cancer

Abstract

Most cancers have many chromosomal abnormalities, both in number and in structure, whereas some show only a single aberration. In the era before molecular biology, cancer researchers, studying both human and animal cancers, proposed that a small number of events was needed for carcinogenesis. Evidence from the recent molecular era also indicates that cancers can arise from small numbers of events that affect common cell birth and death processes.

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Figure 1: Log–log plots of cancer death rates in males (per 100,000) versus age, showing a linear relationship that is consistent throughout the developed world.
Figure 2: A comparison of karyotypes.
Figure 3: One-hit and two-hit curves for retinoblastoma.
Figure 4: Two-hit tumour formation in both hereditary and nonhereditary retinoblastoma.
Figure 5: A possible five-hit scenario for colorectal cancer, showing the mutational events that correlate with each step in the adenoma–carcinoma sequence.

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DATABASES

CancerNet:

breast cancer

Burkitt's lymphoma

chronic myelogenous leukaemia

colorectal carcinomas

osteosarcoma

retinoblastoma

 LocusLink:

ABL

AKT

APC

MLH1

MSH2

MYC

NF1

NF2

HRAS

RB1

TGFBR2

TP53

WT1

 Medscape DrugInfo:

Gleevec

 OMIM:

familial adenomatous polyposis

hereditary non-polyposis colorectal cancer

Li–Fraumeni syndrome

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Knudson, A. Two genetic hits (more or less) to cancer. Nat Rev Cancer 1, 157–162 (2001). https://doi.org/10.1038/35101031

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