Somatic Genetic testing in cancer Flashcards
What is the most common specimen for germline testing?
Blood–specifically nucleated leukocytes or white blood cells
What are some exclusionary reasons to not use blood for germline testing?
Transplants (bone marrow or organ), low white blood cell counts, high levels of malignant cells circulating
What are tissues used for somatic testing?
Formalin-fixed paraffin-embedded tissue sample, frozen tissue, cytology specimen, stool
What are some hurdles to somatic testing?
Tumor purity and heterogeneity
What type of profile could be clinically used to guide treatment decisions?
Molecular profiling
What types of indications are FDA approved for molecular precision oncology?
BRAD/MEK inhibitors for melanoma with BRAF V600E variant
KRAS and NRAS variants in colorectal cancer associated with anti-EGFR antibody resistance
What are the two precision oncology approaches?
Tumor biopsy compared to normal tissue (DNA/RNA sequencing of tumor tissue), liquid biopsy (blood for ctDNA sequencing)
Describe sequencing depth
the number of sequencing reads at a given locus
Describe sequencing breadth
The number of targeted loci with sequences aligned
Describe allelic fraction
proportion of sequence reads derived from alternative allele at a locus in a sample
Describe reference allele
Allele at that locus in the reference genome
Describe alternative allele
non-reference allele identified in the sample
Describe the fractions expected for the allelic fraction: homozygous, heterozygous, mosaic/somatic variant
Homozygous: 100%
Heterozygous: ~50%
Mosaic/somatic variant: <30%
What are some limitations of tumor biopsy analysis
Snapshot in time, selection bias from tumor heterogeneity can skew results, samples can have a high fraction of non-tumor cells, samples could be difficult to obtain, difficult to obtain longitudinal data
