Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma

@article{Barr1993RearrangementOT,
  title={Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma},
  author={Frederic G. Barr and Naomi Galili and John Holick and Jaclyn A. Biegel and Giovanni Rovera and Beverly S Emanuel},
  journal={Nature Genetics},
  year={1993},
  volume={3},
  pages={113-117}
}
We have determined that PAX3 (found previously to be mutated in Waardenburg syndrome) is the chromosome 2 locus rearranged by the t(2;13)(q35;q14) translocation of the paediatric solid tumour alveolar rhabdomyosarcoma. The rearrangement breakpoints occur within an intron downstream of the paired box and homeodomain–encodingregions. Upstream PAX3 sequences hybridize to a novel transcript in t(2;13)–containing lines. Cloning and characterization of this novel transcript indicate that the… 
Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma
TLDR
Findings indicate that the t(2;13) generates a potentially tumorigenic fusion transcription factor consisting of intact PAX3 DNA binding domains, a truncated fork head DNA binding domain and C–terminal FKHR regions.
The role of chimeric paired box transcription factors in the pathogenesis of pediatric rhabdomysarcoma.
TLDR
The findings indicate that the genetic changes in these tumors result in high levels of chimeric transcription factors that are hypothesized to inappropriately activate transcription of genes with PAX DNA-binding sites and thereby induce tumorigenic behavior.
A molecular genetic investigation of rhabdomyosarcoma
TLDR
Mutation analysis of tumour samples and cell lines from patients with embryonal and alveolar rhabdomyosarcoma suggests that there are no subtle disease associated mutations within the P AX3 gene that could contribute towards the neoplastic state.
Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma
TLDR
These translocations alter biological activity at the levels of protein function, gene expression, and subcellular localization with the cumulative outcome postulated to be aberrant regulation of PAX3/PAX7 target genes.
In vivo amplification of the PAX3-FKHR and PAX7-FKHR fusion genes in alveolar rhabdomyosarcoma.
TLDR
Findings indicate that translocation and amplification can occur sequentially in a cancer to alter both the structure and copy number of a gene and thereby activate oncogenic activity by complementary mechanisms.
Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma.
TLDR
Formation of chimeric transcription factors has now been implicated in diverse human tumors of myogenic, hematopoietic, neuroectodermal, and adipocytic origin, suggesting that transcriptional deregulation is a common mechanism of tumorigenesis.
CHIMERIC PAX PROTEINS IN RHABDOMYOSARCOMA Expression Characteristics of Wild-Type and Chimeric Products
TLDR
The findings indicate that the genetic changes in these tumors result in high levels of chimeric transcription factors that are hypothesized to inappropriately activate transcription of genes with PAX DNA-binding sites and thereby induce tumorigenic behavior.
Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma.
TLDR
These findings indicate that this t(1;13) rearranges PAX7 on chromosome 1 and fuses it to FKHR on chromosome 13, which results in a chimeric transcript which is similar to the 5' PAX3-3' FK HR transcript formed by the t(2;13), and postulate that these translocations create similar chimeric transcription factors that alter expression of a common group of target genes.
Clinical utility gene card for: Alveolar rhabdomyosarcoma
1.3 Name of the analysed genes or DNA/chromosome segments FORKHEAD BOX O1A, FOXO1A (formerly FORKHEAD IN RHABDOMYOSARCOMA, FKHR), gene locus: chromosome 13q14.1 PAIRED BOX GENE 3, PAX3, gene locus:
...
...

References

SHOWING 1-10 OF 21 REFERENCES
Chromosomal sublocalization of the 2;13 translocation breakpoint in alveolar rhabdomyosarcoma
TLDR
This work confirmed that the FMS‐like tyrosine kinase gene (FLT), previously localized to 13q12 by in situ hybridization, is located proximal to the breakpoint, and demonstrated that FLT is not a target for disruption by this tumor‐specific translocation.
Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours
TLDR
Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation.
A specific chromosomal abnormality in rhabdomyosarcoma.
A specific chromosomal abnormality, t(2;13)(q35;q14), was discovered in five cases of advanced rhabdomyosarcoma. It was identified directly in cells that had metastasized from bone marrow in one
Molecular and cytogenetic analysis of chromosomal arms 2q and 13q in alveolar rhabdomyosarcoma
TLDR
The characteristic translocation between chromosomes 2 and 13, t(2;13)(q35;q14), has been identified in both cases of alveolar rhabdomyosarcoma and no evidence of rearrangement within or near these genes is indicated.
Molecular definition in a somatic cell hybrid of a specific 2:13 translocation breakpoint in childhood rhabdomyosarcoma.
TLDR
A consistent, balanced, reciprocal chromosomal translocation t(2:13) (q35:q14) has been identified in alveolar rhabdomyosarcoma and a region of 13q14 of approximately 28mB is defined which contains the breakpoint associated with this rearrangement.
A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family.
TLDR
A 14 bp deletion in the paired domain encoded by exon 2 of HuP2 in an Indonesian family segregating for WS1 is reported and it is proposed that the WS1 phenotype in this family is due to loss of function ofHuP2.
Chromosomal analysis of sixteen human rhabdomyosarcomas.
TLDR
Although the eight tumors had no common structural abnormality, trisomy 2 was present in all, and in the nine embryonal tumors studied, one had a normal karyotype, and eight were abnormal.
An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome
TLDR
A mutation causing Waardenburg's syndrome as well as a mutation causing a form of congenital deafness was found in the HuP2 gene, a member of the paired domain family of proteins that bind DNA and regulate gene expression.
...
...