[ES]En este artículo describimos una nueva serie de traslocaciones cromosómicas causanes del linfoma anaplásico de célula grande. En estas traslocaciones, TFG puede utilizar una variedad de puntos de ruptura intrónicos en reordenamientos de ALK que generan proteínas de fusión de diferentes pesos moleculares, pero con un potencial de transformación similar al de NPM-ALK.
[EN]Anaplastic large cell lymphomas are associated with
chromosomal aberrations involving the anaplastic
lymphoma kinase (ALK) gene at 2p23 that result in
the expression of novel chimeric ALK proteins with
transforming properties. In most of these tumors, the
t(2;5)(p23;q35) generates the NPM-ALK fusion gene.
However, several studies have now demonstrated that
genes other than NPM may be fused to the ALK gene.
We have recently described two different ALK rearrangements involving the TRK-fused gene (TFG) in
which the same portion of ALK was fused to different
length fragments of the 5 TFG region. These two
rearrangements encoded chimeric proteins of 85 kd
(TFG-ALKS) and 97 kd (TFG-ALKL), respectively. In
this study, we have identified a new ALK rearrangement in which the catalytic domain of ALK was fused
to a larger fragment of the TFG gene (TFG-ALKXL),
encoding for a fusion protein of 113 kd. Genomic
analysis of these three TFG-ALK rearrangements revealed that the TFG breakpoints occur at introns 3, 4,
and 5, respectively, whereas the ALK breakpoints
always occur in the same intron. No homologous regions or known recombination sequences were found
in these regions. Transfection experiments using
NIH-3T3 fibroblasts showed a similar transforming
efficiency of TFG-ALK variants compared with NPMALK. In addition, in common with NPM-ALK, the TFGALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC- . In conclusion,
these findings indicate that the TFG may use a variety
of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular
weights, but with similar transforming potential than
NPM-ALK.
