Cancer Genomics - Genomic Testing in Cancer - Week 10

Question 1

why do a genetic test in cancer?

Answer 1

confirm a diagnosis
allow pre-symptomatic testing
accurate assessment of genetic risk
change/devise treatment plan
information about prognosis and management

Question 2

Commonly used technologies

Answer 2

Single gene sequencing

Next generation sequencing of gene panels

Question 3

Multigene next generation sequencing panels are frequently used in the diagnosis of

Answer 3

hereditary cancers

Question 4

Majority of hereditary cancer has an apparently

Answer 4

autosomal dominant transmission of specific cancer type(s)
Early age of onset multiple priory care cancers in an individual
Bilateral or multifocal cancers

Question 5

Over 50 hereditary cancer syndromes

Answer 5

o	Retinoblastoma
o	Li Fraumeni
o	Breast Cancer
o	Colon cancer
	FAP
	Lynch Syndrome
o	Von Hippel Lindau syndrome
o	Multiple endocrine neoplasia Type 1 and 2
o	Cowden Syndrome

Question 6

Previously, when an inherited cancer syndrome was suspected

Answer 6

The gene/genes known to be responsible were screened

Pre-screening (SSCP, HRM)

Sanger sequencing exon by exon, gene by gene

Question 7

Previously, Considerations with the pre-screening and gene by gene approaches

Answer 7

• Testing criteria (Bethesda criteria, Amsterdam criteria, Manchester score)
• Waiting times (in 2005 the waiting tikme to get a BRCA1 and BRCA2 screen was more than 3 years in some places in the UK
• Cost if more than 1 gene involved in a syndrome which one first?
• Overlapping diagnosis
o Breast cancer in Lynch syndrome and Cowden Syndrome (in addition to BRCA1 and BRCA2)
o Phaeochromacytoma in VHL and MEN2

Question 8

Now,

Answer 8

• Now with the advent of NGS we have multi-gene panels to test for inherited cancer syndromes…
o Cheaper
o Quicker
• Panels are either available commercially or custom designed

Question 9

Single gene sequencing tests in cancer. Pre-symptomatic testing

Answer 9

• Testing for unaffected members of families affected by inherited cancer syndromes where a mutation has previously been identified
• Allows intensive screening of at risk patients and prophylaxis
i.e. presymptomatic test for MEN2

Question 10

Targeted therapy in cancer (pharmacogenomics)

Answer 10

Sequencing of specificc genes to inform treatment

Question 11

Targeted therapy in cancer (pharmacogenomics) Melanoma -

Answer 11

Vemurafenib (BRAF kinase inhibitor) indicated in tumours with V600E mutation in BRAF

Question 12

Targeted therapy in cancer (pharmacogenomics) Colorectal cancer -

Answer 12

Cetuximab (Anti-EGFR antibody) not indicated in those patients with KRAS mutations

Question 13

Targeted therapy in cancer (pharmacogenomics) Non-small cell lung cancer -

Answer 13

Gefitinib (Tyrosine kinase inhibitor) in patient with a mutation in the TK domain of EGFR gene

Question 14

From Sanger sequencing to

Answer 14

targeted NGS panels

Question 15

What about research?

Answer 15

Sequencing technologies are used extensively in cancer research:

1. Cancer causing mutations
2. Therapeutic targets
3. Prognostication