in advance of 1000 genomes, can we use mitochondrial dna sequencing? advantages: small size (16kb), and maternally inherited (allows human phylogeny)
- Andrew Su
mitochondria have known role in cancer, but unclear if the mito genome (and mutations therein) are relevant
- Andrew Su
method: compare tumor and normal mtDNA -- patient-matched. --> mutational landscape --> eliminate SNPs in normals --> find high recurrence. BUT, nothing found...
- Andrew Su
method 2: from mutational landscape, look for co-mutations: two patients with multiple mutations observed
- Andrew Su
one "flip-flop" observed -- mutation in tumor in one patient and in normal in another -- bi-stability?
- Andrew Su
compare evolution in normal population as reference; create trees via nieghbor joining, create inner nodes, find deepest branch with mutation; conclusion: cancer uses snps that arise early in human evolution
- Andrew Su
relates to african vs european haplotypes?
- Andrew Su
conclusion: mtDNA is under selection in cancer; strategy of finding multiple SNPs in subset of tumors; functional prediction of 25 mtDNA snps
- Andrew Su
philosophilcal question -- are tumors different species? unicellular parasites?
- Andrew Su
A tumor is like a parasite branching off as a separate species from the human
- Michael Kuhn
Some cancers have actually become infectious, like a separate species. Eg Tasmanian devil
- Michael Kuhn