Charuwan Akewanlop, MD
Division of Medical Oncology
Department of Medicine
Faculty of Medicine Siriraj Hospital
Scope
Overview of Molecular Genetics of Cancer
Principles of Systemic Therapy
“Cancer is, in essence, A Genetic Disease”
Gene mutations lead to cancer Predisposing mutations
Somatic mutations
Cancer
Cancer Arises From Gene Mutations
Germline mutations |
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Somatic mutations |
Parent Child
Mutation |
All cells |
Somatic |
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affected in |
mutation (eg, |
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in egg or |
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offspring |
breast) |
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sperm |
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l l l
Present in egg or sperm
Are heritable Cause cancer family syndromes
l
l
Occur in nongermlinermline tissues
Are nonheritablele
Multi-Step Carcinogenesis (e.g. Colon Cancer)
Loss of |
Activation |
Loss of |
Loss of |
Other |
APC |
of K-ras |
18q |
TP53 |
alterations |
Normal |
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Hyper- |
Early |
Inter- |
Late |
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MetastasisMetastasis |
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proliferative |
mediate |
Carcinomainoma |
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epithelium |
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adenoma |
adenoma |
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epithelium |
adenoma |
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Adapted from Fearon ER. Cell 61:759, 1990
Tumors Are Clonal Expansions
Normal
Tumor