Kuliah Neoplasia

Harliansyah, Ph.D
2016

General Model of Cell Kinetics

PROLIFERATION

growth fraction
self-renewal
capacity

G2

differentiation

S
G1

APOPTOSIS

Molecular Basis of Neoplasia:

ity
d
re
e
H

Proto-oncogene

i
d
Ra
c
n
V-O

n
o
i
at
e
h
C

l
a
c
mi

er
h
t
O

Oncogene

Chromosomal changes in the genome of cancer

cells: tip of the iceberg
Deletion

Terminal
Deletion

Reciprocal
translocation

Duplication

Insertion

Inversion

Ring
Chromosome

Robertsonian
Translocation

Isochromosomes

http://www.tokyo-med.ac.jp/genet/cai-e.htm15

Nucleotide changes in the genome of cancer

cells: unseen site of the iceberg
Nucleotide
Deletions

Nucleotide
Insertions

Nucleotide
Substitutions

16
http://www.tokyo-med.ac.jp/genet/cai-e.ht

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

DCC (18q)
cell surface
interactions

Familial

Sporadic

unknown

colorectal
cancer

WT1 (11p)

transcription

Wilms tumor

lung cancer

Rb1 (13q)

transcription

retinoblastoma
carcinoma

small-cell lung

p53 (17p)

transcription
Li-Fraumeni
breast, colon,
syndrome
& lung cancer

BRCA1(17q)

transcriptional

breast cancer
tumors

breast/ovarian

BRCA2 (13q) regulator/DNA repair

23

DNA Loss in cancer cells: beyond coincidence ...

Early Brain Tumor
(Astrocytoma Stage II)

Advance Brain Tumor

Glioblastoma Multiform (Stage IV)

26

Chromosomal loss:
Mostly, it is a sign
for the loss of a
tumor suppressor
gene
CDKN2
locus
PTEN
locus
RB1
locus
???
locus
p53
locus
27

TissueCell#
=
CellProliferation

Oncogenes

Tumor
Suppressor
Genes

__

CellDeath

Pro
Apoptotic
Factors

Anti
Apoptotic
Factors