2009 Vienna - European Society of Human Genetics

Cancer genetics
P06.168
characterization of a novel EtV6-NtRK3 Fusion transcript in
Acute myeloid Leukemia
W. Kranewitter, J. Kralik, G. Tschurtschenthaler, R. Marschon, G. Webersinke;
Hospital Barmherzige Schwestern, Linz, Austria.
Introduction: ETV6 transcription factor is frequently rearranged in diverse
tumors forming a variety of fusion genes. We could identify a
novel ETV6-NTRK3 gene fusion in an AML patient.
Methods: AML was diagnosed morphologically and by flow cytometry.
Conventional karyotyping demonstrated a t(12;15)(p13;q25) confirmed
by whole chromosome paints. ETV6 break apart FISH proved an involvement
of this gene. 3´RACE-PCR was performed to characterize
the unknown 3´end of the fusion product. PCR products were subsequently
cloned and sequenced. The rearrangement was verified by
fusion-specific reverse transcriptase PCR.
Results: RACE-PCR and sequencing analysis identified NTRK3 (neurotrophic
tyrosine receptor kinase 3) as in-frame fusion partner of the
ETV6 gene. NTRK3 transcripts encode either catalytically active proteins
or truncated isoforms that lack the intracellular kinase domain.
The ETV6-NTRK3 transcript fuses ETV6 exons 1 through 5 with exons
13b and 14b of a truncated NTRK3 isoform and encodes a protein that
contains the amino-terminal HLH domain of the ETV6 protein and Cterminal
amino acids 529-612 of the NTRK3 protein.
Conclusions: We identified a novel ETV6-NTRK3 gene fusion in a patient
with minimal differentiated AML. Interestingly, this chromosomal
rearrangement is documented in a significant fraction of patients with
secretory breast cancer and congenital fibrosarcoma.
P06.169
sibs‘ birth defects in families with acute leukemia
N. Kitsera1 , O. Hnatejko1 , R. Polishchuk2 ;
1 2 Institute of Hereditary Pathology, Lviv, Ukraine, Regional Specialized Children’s
Clinic, Lviv, Ukraine.
Clinical and genealogical analysis was conducted in 240 families of
the Lviv region (Ukraine) which had two and more children. The basic
group was made with 120 families, which had children with acute leukemia.
Children were treated in hematology department of the Lviv Regional
children’s specialized clinical hospital 1994 - 2008 concerning.
The age of children was from 3 months till 16 years (3,8±1,9 years).
Research carried by a method “ case - control “. Among 120 families
of the basic group, which had the two and more children, we observed
11 families (9,2 %), where, except for cancer at proband, sibs had
birth defects. In control group the birth defects at sibs met in 3 ( 2,5%)
cases (P