Genetics and Genomics in Cancer 2013: How Genomics is Changing Cancer Care, Dr. Lea Velsher

Genomics and Cancer 2013

How Genomics is Changing Cancer Care

Faculty/Presenter Disclosure

Faculty: Dr. Lea Velsher

Advisor for Thunder Bay Genetics, NRGP

Physician at North York General Hospital, Genetics

Consultant in Genetics for Medcan Clinic

No conflicts of interest to declare

Learning

• Explain how the genetics of sporadic and hereditary cancers differ

• Review features that suggest an inherited cancer risk

• Discuss how genomics is being integrated into cancer diagnosis and treatment

• Somatic Cells • Germ Cells

Epigenomics

• Method for turning genes ‘off’ or ‘on’

• Reversible changes to chromosomes

• No mutations in the DNA code itself

• Environment may alter epigenomics in cells

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Epigenomics: regulating expression of genes

Cancer is a genetic disease: accumulation of mutations and

epigenomic changes in somatic cells

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What patterns make us think of a hereditary risk?

• Family history

• Personal history

• Pathology

• Unusual features

Family History

• 3 or more close relatives with cancer

• Cancer < 50 years old

• Clusters of certain cancer types

• Person has >1 primary cancer

52 y.o. woman Ductal Breast Cancer

3 2

Breast 75Breast 60

Breast 38

Personal history

Colon cancer 29 years old

Pathology of the tumour

• Medullary Breast Cancer:– Triple negative in premenopausal woman– Consider BRCA1 testing

• Right sided mucinous undifferentiated colon cancer– Consider doing Immunohistochemistry for

Lynch (HNPCC)

• Medullary thyroid cancer– Consider genetic testing for MEN2

Unusual findings

Multiple polyps on colonoscopy

• A benign neoplasm of sebaceous tissue, with a predominance of mature secretory sebaceous cells.

Sebaceous Adenoma

Most cancer is sporadic

We can use the genomic changes unique to the cancer for:•Prognosis •Therapy•Screening

Genomic analysis of the tumour cells

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For ER +, Node - tumours

Screening for cancer using cancer biomarkers

Genetic biomarkers as a screen

• Methylated Septin 9

test

– Blood test

– Looks at a gene that is

methylated in colon

cancer

– Sensitivity and specificity

maybe 60 - 85%

Targeted Therapy

Altered genome leads to altered protein products

Target the cancer cells based on their altered genotype and phenotype

Pharmacogenomics

• Germ line polymorphisms

• Alter pharmacokinetics/dynamics of

chemotherapy agents

• UGT1A1 – homozygous SNP reduces

activity

– Increases toxicity of Irinotecan

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E.G. CYP2D6 and Tamoxifen

What will the future hold?

• Cheaper, simpler, faster testing

• Incorporation of genomic markers into risk algorithms

• Targeted ‘personalized’ treatment based on genomic information

• Pharmacogenomic testing at point of care

Summary Points

• All cancer is ‘genetic’ but only a small number of cases are ‘hereditary’

• Genomic and epigenomic changes within the cancer (somatic mutations) can be used in screening and treatment

• A person’s genomic (germ line variations) make up may influence treatment

Thank You