Medical Biochemistry

Cancer Molecular
Signatures
Pedro Santiago, Ph.D.
• Lecture Objectives:
– After this lecture, students
should be able to explain:
• What is a Cancer Molecular
Signature
• What is a Biomarker
• Some of the techniques
used in pathology
laboratories to detect
Biomarkers and Molecular
Signatures
• How can Molecular
Signatures & Biomarkers
assist clinicians in the
diagnosis and management
of cancer
• The Concept of Precision
Medicine and Targeted
Therapy
– Basic Concepts:
• A cancer molecular
signature is a molecular
change (or a collection of
molecular changes or
biomarkers) detected at
the DNA, mRNA, protein
or PTM level, that is
clinically informative.
• Oncologists can use such
signatures to predict
patient survival, choose a
specific therapy
(Precision Medicine or
Targeted Therapy), predict
resistance…
– Basic Concepts:
• … monitor treatment
response, predict possible
courses of disease
progression, assess cancer
risk, classify cancer sub-
types, etc.
• These signatures are usually
detected by various
genetic, epigenetic,
molecular and proteomic
tools. Their detection
mostly relies on obtaining
tissue samples usually from
a biopsy.
• Refer to Devlin´s book
pages 1023- 1024, and
Figure 24.21, for a brief
explanation on how
signatures are obtained.
 Stratifying Breast Cancers by Gene
Transcriptional Profiling: Overall Survival
Prediction

12%

42%

Figure 16.4a The Biology of Cancer (© Garland Science 2007)

 Stratifying Breast Cancers by by Gene
Transcriptional Profiling: Overall Survival
Prediction

Kaplan-Meier Plot
Figure 16.4b The Biology of Cancer (© Garland Science 2007)
 Gene Expression Analysis To
Stratify Diffuse Large B-cell
Lymphomas (DLBCLs)
1. PMBL, primary
mediastinal; 2. GCB,
germinal center B-cell; 3.
ABC, activated B-cell like

Figure 16.5a The Biology of Cancer (© Garland Science 2007)

Different DLBCL Sub-types
Have Different Outcomes

Treatment approaches can also vary

among different subtypes
Figure 16.5b The Biology of Cancer (© Garland Science 2007)
Different Mutations Define
Different Stages of Pancreatic
Cancer Progression

Figure 16.9 The Biology of Cancer (© Garland Science 2007)

Twist Expression Strongly
Affects Melanoma Patient
Overall Survival

Figure 14.29b The Biology of Cancer (© Garland Science 2007)

Gene Hyper-Methylation
Landscape of Several Cancer
Types

Figure 7.19 The Biology of Cancer (© Garland Science 2007)

N-myc Gene Copy
Amplification (CNV)
Affects Neuroblastoma
Prognosis

Figure 4.11a The Biology of Cancer (© Garland Science 2007)

N-myc Gene Copy Amplification
Affects Neuroblastoma Prognosis

Figure 4.11b The Biology of Cancer (© Garland Science 2007)

Suppression of p27 Function by
Akt/PKB in Human Breast
Cancer

Figure 8.16a The Biology of Cancer (© Garland Science 2007)

Nuclear p27 Localization
Indicates a Favorable Prognosis
in Human Breast Cancer

Figure 8.16b The Biology of Cancer (© Garland Science 2007)

Amplification of the Cyclin D1
Gene Detected by Fluorescence
In Situ Hybridization

Figure 8.36 The Biology of Cancer (© Garland Science 2007)

Cyclin E Over-Expression
Negatively Affects Patient Survival

Figure 8.38 The Biology of Cancer (© Garland Science 2007)

Amplification of the erbB2/neu
Oncogene In Breast Cancer

Figure 4.6c The Biology of Cancer (© Garland Science 2007)

Amplification of the erbB2/neu
Oncogene Negatively Affects
Breast Cancer Survival

Figure 4.6b The Biology of Cancer (© Garland Science 2007)

 Increased p53 Expression in
Ovarian Cancer

Figure 9.17 The Biology of Cancer (© Garland Science 2007)

Homework: p53 is a tumor suppressor, it is

usually expressed at very high levels in cancer
tissues, paradoxically, that is related to a bad
prognosis. How can you explain that paradox?
How to Prepare For Class &
Exam
– Think about genes that could
be informative biomarkers
– Read a bit about the techniques
(optional)
– Read Devlin book pages 1023-
1024, and Figure 24.21
– Be ready to discuss and
participate in class
– Questions? E-mail me for an
appointment
(psantiago@psm.edu)