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PAE mutation ‘Selfish’
Selfish selection is an oncogenic process
oncogenic process
All PAE genes are
known cancer genes (FGFR2 FGFR3 HRAS RET PTPN11) (MEK1/2, BRAF KRAS...)
Spermatogonial stem cell/progenitor
Spermatozoa
Testicular Tumours (SpS)
Proliferation
Differentiation
FGFR3 p.K650E 2/54
normal tumour
HRAS p.G13R & Q61R/K 7/54
normal tumour
TD II
Costello HRAS p.G12S
Goriely et al, Nat. Genet. (2009); Giannoulatou et al, PNAS (2013)
Seborrheic Keratoses
80-100% of individuals >50yrs Average 70 moles / individual >75yrs
Wide spectrum of FGFR3 mutations in SK
Selfish mutations in benign skin tumours
Page 30 of 102
S249C
S371C
K650E
S249C
Y373C
R248C
Y373C
S249C
K650E
G370C
R248C
G370C
Y373C
K650M
Can we visualise these ‘selfish moles’ directly in the human testis ?
K650E
R248C
K650M
Hafner et al, 2007, J. Inv. Derm 127
R248C
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