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.

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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.

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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:
...

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TLDR
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