Kuliah Neoplasia

Harliansyah, Ph.D
2016
 General Model of Cell Kinetics

PROLIFERATION

growth fraction

self-renewal differentiation
capacity G2 M

G1

APOPTOSIS
 Molecular Basis of Neoplasia:

Proto-oncogene

Oncogene
 Chromosomal changes in the genome of cancer
cells: tip of the iceberg
Deletion Duplication Reciprocal Ring
translocation Chromosome

Terminal Insertion Inversion Robertsonian Isochromosomes

Deletion Translocation

http://www.tokyo-med.ac.jp/genet/cai-e.htm15
Nucleotide changes in the genome of cancer
cells: unseen site of the iceberg
Nucleotide Nucleotide Nucleotide
Deletions Insertions Substitutions

16
http://www.tokyo-med.ac.jp/genet/cai-e.htm
 Type of DNA Mutation

Color Atlas of Genetics. 2nd Ed. Passarge, E. Thieme. Stuttgart, Germany 2001
Molecular basis for risk factors
 TUMOR SUPPRESSOR GENES
Disorders in which gene is affected

Gene (locus) Function Familial Sporadic

DCC (18q) cell surface unknown colorectal

interactions cancer

WT1 (11p) transcription Wilms tumor lung cancer

Rb1 (13q) transcription retinoblastoma small-cell lung

carcinoma

p53 (17p) transcription Li-Fraumeni breast, colon,

syndrome & lung cancer

BRCA1(17q) transcriptional breast cancer breast/ovarian

tumors
BRCA2 (13q) regulator/DNA repair
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DNA Loss in cancer cells: beyond coincidence ...
Early Brain Tumor Advance Brain Tumor
(Astrocytoma Stage II) Glioblastoma Multiform (Stage IV)

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Chromosomal loss:

Mostly, it is a sign
for the loss of a
tumor suppressor
gene

CDKN2
locus

PTEN
locus

RB1
locus
???
locus
p53
locus

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 Tissue Cell #

__
Cell Proliferation Cell Death

Tumor
_ Suppressor Pro Anti
Oncogenes _
Apoptotic Apoptotic
Genes
Factors Factors