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Distinct clones can occur in close proximity
N
FGFR3 p.R248C
FGFR3 c.742C>T (p.R248C)
PTPN11 WT
N
FGFR3 p.R248C
PTPN11 WT
FGFR3 WT
PTPN11 WT
N
FGFR3 p.R248C
PTPN11 c.215C>T (p.A72V)
Germline
Thanatophoric dysplasia type I
Somatic
COSMIC v70 Bladder cancer Skin (SK)
Germline
not reported
p.A72S Noonan syndrome
Somatic
COSMIC v70 Leukemia
N
PTPN11 p.A72V
Testis from 75 yo individual
S20_MAGEA4
FGFR3 p.R248C and PTPN11 p.A72V are mutually exclusive
Selfish selection increases the apparent mutation rate Q: How many genomic sites are subject to selfish selection?
6
5
4
3
2
1 0
Mutations never transmitted / infertility
Many Selfish Mutations?
Selfish mutations (PAE disorders)
Number of genomic locations (log10)
x
?Any mutation that dysregulates SSC behaviour is a candidate selfish mutation?
xxxxx x 10-6 10-5
10-10 10-9 10-8
10-7
Apparent Mutation Rate
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PRECONGRESS COURSE 08 I BARCELONA, SPAIN – 1 JULY 2018 41