Molecular Testing in Cancer Diagnosis Flashcards
hall marks of cancer
unregulated growth
impaired differentiation
invasiveness
metastatic growth
subclones of cancer are important why?
if there are multiple types of clones within a tumor, they may contain varying resistances to treatment
oncogenes
activating genes- dominant mutations
ex- point mutation, gene amplification, translocation
tumor suppressor genes
inactivating mutations- recessive mutations
ex. point mutations, allelic deletion, promoter hypermethylation
challenges of oncology testing
differentiating normal v tumor cell genome
differences between primary vs metastatic tumor
heterogeneity within tissues and tumors
% tumor cell content for accurate testing
recurrence
monitoring tumor load burden
qualitative molecular oncology testing- diagnostic mutation analysis
diagnostic mutation analysis
used to check for lymphoma where DNA is digested with different enzymes and compared to a control to determine where in development the problem is
PCR based version determines clonality- if all cells are from the same clone
HPV qualitative mutation analysis
subtypes 16 and 18 cause cancer in US
sexually transmitted w/o symptoms
99% of cervical cancers have HPV
use of linear array- HPV sample binds probe on strip corresponding to type of HPV
quantitative PCR
the amount of PCR samples being generated is detected via fluorescence to determine starting amount
quicker detection = more to start
therapeutic selection
using genome of cancer and or patient to determine potential treatments
irinotecan
colon cancer drug
oral- metabolized by CPT11 into active metabolite SN38 and inactivated by UGT1A1
polymorphism of TA repeat UGT1A1- people with 7 repeats have a poor response
HER-2 gene
35% of women with breast cancer have amplification of HER2 gene products
eligible for herceptin drug
lung adenocarcinoma
most common carcinoma in non smokers
not advanced until late stage
conventional chemo has little effect
anti-EGFR and anti- ALK therapies are helpful
kRAS
oncogene- activating
associated with smoking in colon cancer
occurs mostly in codons 12 and 13 w/ missense mutations- 7 mutations account for 95% of cases
clinically actionable
clinically actionable and FDA approved application
actionable but off lable use
clinically actionable to select clinical triable
not actionable but therepeutics being developed
