The ETV6 gene is rearranged as a result of translocations involving a wide
variety of chromosomal partners. To date, 12 partner genes for ETV6 have be
en cloned, and a further 23 chromosomal regions have been described. We pre
viously identified a cryptic t(7; 12) with ETV6 involvement in two cases of
infant leukemia. The finding of a third case of t(7; 12), also in an infan
t, prompted a more focussed search based on the common features found in th
ese patients and those reported in the literature. The selection criteria w
ere age at diagnosis < 20 months and the presence of + 19 and/or +8 in the
karyotype; cases with abnormalities of 7q and/or 12p were also considered.
FISH studies using whole chromosome paints and probes for the ETV6 gene rev
ealed a t(7; 12) in 10 out of 23 cases studied. Seven of these had evidence
of ETV6 rearrangement. Of those with ETV6 involvement, six had a 7q36 and
one a 7q22 breakpoint. Importantly, in three cases the 7q36 breakpoint was
within the same PAC, suggesting the existence of a new nonrandom translocat
ion. However, in at least one patient the 7q36 breakpoint was different. Th
e identification of the 7q partner genes will determine whether it is the d
isruption of ETV6 alone, or the formation of fusion genes, that is importan
t for leukemogenesis in these patients. As both 7q36 and 7q22 are critical
regions of gene loss in del(7q) leukemias, the identification of partner ge
nes from these regions may also be important in understanding the pathogene
sis of these diseases, (C) 2000 Wiley-Liss, Inc.