Download - Molecular Biology for Clinicians
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Moleculf
CliniProf Ernesto
Instituto Oncolo
Universidad
r Biologyr
iansGil Deza MD
ico Henry Moore
de Salvador
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Objectives
Definition
Pathogenesis
Clinical applications
Objec
tives
Definition
Pathogenesis
Clinical applications
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Molecular Diagnostic Tools
DNA
Citogenetics
FISH and CISH
CGH
CGH arrays
SNPs
PCR sequencing
Southern blot
Microsatelliteinstability
Microarray
Molecular Dia
gnostic Tools
RNA
Transc. Pro iling
Northern blot
RT-PCR
ISH, FISH & CISH
Proteins
Western blot
2D electro horesis
MALDI-T F
S LDI-T F
IHC
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Some pr blems
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Sample tissue
Gross Tumor Specimen
Fine Needle Aspiration
Microdissection of Pure Tumor Cells
Paraffin block
Frozen sample
Fresh tissue
Sample tissue
Gross Tumor Specimen
Fine Needle Aspiration
Microdissection of Pure Tumor Cells
Paraffin block
Frozen sample
Fresh tissue
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Huma
Nuclear
3000 Mb
~30.000 genes
Genes
30 %
Extragenetic
70%
Encoded Non encoded
L10% 90%
Quan
Genome
Mitocondrial
16.6 kb
37 genes
ow number
of copies
Higher number
of copies
80%20%
itative
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Statistics
0 000 50 000 genetic features
for only few outcomes:
Response/No responce
Recurrence/No
recurrence
Survival/death
Greater chances of false positive
results
Statistics
0 000 50 000 genetic features
for only few outcomes:
Response/No responce
Recurrence/No
recurrence
Survival/death
Greater chances of false positive
results
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Patho enesis
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Oncog
Hannahan and W
enesis
einberg Cell 2000
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Preinv
Invas
Genetic in
sive
ive
tability
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Clinical a plications
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Clinical applications
Risk predictionCancer diagnosis
Differential diagnosis
Tumor subtypification
Pharmacogenetics
Prediction of clinical outcomes
Novel targeted therapeutics
Modified
orkman Johnsto JCO October 10th 005
Clinical applications
Risk predictionCancer diagnosis
Differential diagnosis
Tumor subtypification
Pharmacogenetics
Prediction of clinical outcomes
Novel targeted therapeutics
Modified
orkman Johnsto JCO October 10th 005
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Risk prediction
ow penetrance high risk
BRCA1
BRCA
High penetrance low risk
Risk prediction
ow penetrance high risk
BRCA1
BRCA
High penetrance low risk
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Ethica issues
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Cancer diagnosis
Differencial diagnosis ADH DCIS CDI
DNA microarray of ductal lavage
Nanoparticles and blood products
Cancer diagnosis
Differencial diagnosis ADH DCIS CDI
DNA microarray of ductal lavage
Nanoparticles and blood products
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Tu
Subtypi
or
ications
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Disagree ent in ICH
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Molecular Breast Canc r Subtype Dendrogram
Carey - ASCO 2005
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Te
Classification
to
equirements
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Prog osis
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2000
Prognostic and
500 BC1870
atural history
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0
20
40
60
80
100
120
Bajo
Inte
rmedio
Alto
3G+
10G+III
0
20
40
60
80
100
120
Bajo
Inte
rmedio
Alto
3G+
10G+III
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Due to the nature of t
21 gene assay, which areand ER-related genes, it
assay is an expensive replacement fo
ass
Paik and K
e genes included in the
ainly proliferation genescould be argued that the
r ER and Ki67 inmunohistochemical
ys
m, page 21
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Molecular predictive
factors
ER
PR
Her
All are good NEGATIVE predictors
Molecular predictive
factors
ER
PR
Her
All are good NEGATIVE predictors
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Expectations and reality
e canIdentify 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
Can we save lives cure more or take care of our
patients better than we do actually?
Expectations and reality
e canIdentify 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
Can we save lives cure more or take care of our
patients better than we do actually?
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Concl
Sir illiam Osler
1880
usion
I have loved no darkness,
Sophisticated no truth,
Nursed no delusion,Allowed no fear
Aequanimitas
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Thank youfor your
very muchttention