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Molecular Biology For Clinicians
Molecular Biology For Clinicians
for
Clinicians
Prof Ernesto Gil Deza MD
Instituto Oncologico Henry Moore
Universidad de Salvador
Objectives
Definition
Pathogenesis
Clinical applications
Molecular Diagnostic Tools
DNA RNA
Citogenetics Transc. Profiling
FISH and CISH Northern blot
CGH RT-PCR
ISH, FISH & CISH
CGH arrays
SNPs
PCR sequencing Proteins
Western blot
Southern blot
2D electrophoresis
Microsatellite MALDI-TOF
instability
SELDI-TOF
Microarray IHC
Molecular Biology
Some problems...
Sample tissue
Paraffin block
Frozen sample
Fresh tissue
Quantitative
Human Genome
Nuclear Mitocondrial
3000 Mb 16.6 kb
~30.000 genes 37 genes
Genes Extragenetic
30 % 70%
80%
20%
Response/No responce
Recurrence/No recurrence
Survival/death
• Greater chances of false positive results
Pathogenesis
Oncogenesis
Preinvasive
Invasive
Clinical applications
Clinical applications
Risk prediction
Cancer diagnosis
Differential diagnosis
Tumor subtypification
Pharmacogenetics
BRCA1
BRCA2
Texto
Prognosis
Prognostic and natural history
aj
20
40
60
80
0
o
In
te
rm
ed
io
A
lto
3
G
+
10
G
+
III
“Due to the nature of the genes included in the
21 gene assay, which are mainly proliferation genes
and ER-related genes, it could be argued that the
assay is an expensive replacement for ER and Ki67 inmunohistochemical
assays”
Paik and Kim, page 21
Molecular predictive
factors
ER
PR
Her2
• All are good NEGATIVE predictors.
Expectations and reality
•We can...
Identify hallmarks in tumorigenesis.
Classify tumors according to molecular subtypes
Predict high risk in a few patients
Avoid toxicity in some patients
Design more sophisticated predictive tools
•But...
Aequanimitas