In Vivo Amplification of the PAX3-FKHR and PAX7-FKHR Fusion Genes in Alveolar Rhabdomyosarcoma

Barr, Frederic G.; Nauta, Lauren E.; Davis, R. J.; Schäfer, Beat W.; Nycum, Lynn M.; Biegel, Jaclyn A.

doi:10.1093/hmg/5.1.15

Cited by 136 publications

(85 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…41 Several amplification mechanisms have been proposed, that is, looping out of extra chromosomal sequences 42 without evidence of chromosomal rearrangements, breakage-fusion-bridge cycles that can be triggered by fragile site induction 43 and a translocationdeletion-amplification model. 44,45 Most of these mechanisms rely on unequal segregation of chromosome sequences during mitosis.…”

Section: Discussionmentioning

confidence: 99%

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

Cauwelier

Cavé

Gervais³

et al. 2006

Leukemia

View full text Add to dashboard Cite

Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRb) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRb-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRb-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRb-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRb-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRb-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRb-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

Cauwelier

Cavé

Gervais³

et al. 2006

Leukemia

View full text Add to dashboard Cite

show abstract

“…Approximately 80% of all new diagnosed cases of RMS are ERMS (60%) or ARMS (20%). More than 90% of the ARMS are characterized by a translocation t(2;13)(q35;q14) or t(1;13)(q36;q14), which results in a chimaeric transcript encoding a fusion protein consisting of the intact PAX3 or PAX7 DNA binding domain and the distal half of the fork head domain of the FKHR gene (Barr et al, , 1995Galili et al, 1993;Davis et al, 1994). ERMS is frequently characterized by LOH of chromosome 11p15.5 and these LOH studies de®ne the putative TSG distal to D11S988 locus (Besnard-GueÂ rin et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Allelotype of pediatric rhabdomyosarcoma

et al. 1997

View full text Add to dashboard Cite

An allelotype covering all autosomes was constructed for the embryonal form of childhood rhabdomyosarcoma (ERMS) in order to identify regions encompassing tumorsuppressor genes (TSG) involved in ERMS. Thusfar most studies were focussed on chromosome 11p15.5, which frequently shows loss of heterozygozity (LOH) in embryonal tumors like RMS and Wilms' tumor (WT). In this study we show that, besides LOH of chromosome 11p15.5 (72%), LOH of chromosome 16q was present in 54% of the tumors analysed. Delineation of these two regions shows that the smallest region of overlap (SRO) for chromosome 11 was between D11S988 and D11S922. This region, estimated to be 7 cM and 3-5 Mb, is also the location of the putative Wilms' tumor WT2 TSG. It contains several genes including IGF2 and potential tumorsuppressor genes like H19 and p57 kip2 , which might contribute to the carcinogenesis of RMS. Analysis of chromosome 16q LOH de®ned the SRO between D16S752 and D16S413. LOH of chromosome 16 is also found in other tumors, including WT. Our data suggest that genes involved in the development of RMS and WT may not only be similar for chromosome 11 but also for chromosome 16.

show abstract

“…Most aRMS express PAX3-FKHR or PAX7-FKHR fusion proteins resulting from [t(2;13)(q35;q14)] or [t(1;13)(p36;q14)] translocations, respectively. [1][2][3] Although a frequently affected chromosomal locus in eRMS has been defined (11p15.5), specific gene(s) or a fusion transcript have not been identified. 4 Ewing's sarcomas (EWS) and the related, more differentiated peripheral neuroectodermal tumors (PNET) are the 2nd most common primary osseous malignancies in childhood and adolescence.…”

mentioning

confidence: 99%

Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing's sarcoma

Baer

Nees

Breit

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

Using Affymetrix oligonucleotide microarrays, we analyzed mRNA gene expression patterns of 12 primary pediatric rhabdomyosarcomas (RMS) and 11 Ewing's sarcomas (EWS), which belong to the small round blue cell tumors (SRBCTs). Diagnostic classification of these cancers is frequently complicated by the highly similar appearance in routine histology, and additional molecular markers could significantly improve tumor classification. A combination of three independent statistical approaches (t-test, SAM, k-nearest neighborhood analysis) resulted in 101 highly significant probe sets that clearly discriminate between EWS and RMS. We identified novel marker transcripts that have not been previously associated with either RMS or EWS yet, including CITED2, glypican 3 (GPC3), and cyclin D1 (CCND1). Expression levels for selected candidate genes were validated by quantitative real-time reverse-transcription PCR. Furthermore, to identify biologically meaningful trends, functional annotations were assigned to 946 genes differentially expressed between EWS and RMS (t-test). Genes involved in protein biosynthesis (n ‫؍‬ 28) and complex assembly (n ‫؍‬ 9), lipid metabolism (n ‫؍‬ 23), energy generation (n ‫؍‬ 22), and mRNA processing (n ‫؍‬ 11) were expressed significantly higher in EWS. Thus, functional annotation of tumor-specific genes reveals detailed insights into tumor biology and differentiation-specific expression patterns and gives important clues related to the possible cellular origin of these pediatric tumors. Small round blue cell tumors (SRBCTs) are frequently difficult to distinguish by standard histology or, sometimes, even by immunohistochemistry. Rhabdomyosarcoma (RMS) and Ewing's sarcomas (EWS) are common pediatric solid tumors that belong to this group that also includes neuroblastoma and Burkitt's lymphoma. However, the correct diagnosis of SRBCT tumors is essential since treatment regimens, response to therapy and prognosis may differ markedly. Therefore, molecular techniques are increasingly implemented for the diagnostic distinction of SRBCT tumors, including EWS and RMS. Progress in recent years includes the identification of characteristic tumor-specific chromosomal translocations, resulting in the expression of aberrant, oncogenic fusion proteins.RMS is the most common pediatric soft tissue sarcoma and can be histologically subdivided into the more prevalent embryonal (eRMS) and the more aggressive alveolar rhabdomyosarcoma (aRMS). ARMS have an unfavorable prognosis due to a tendency to early relapses and frequent failure of chemotherapy. This is reflected by 5-year survival rates ranging between 20 -50%. Most aRMS express PAX3-FKHR or PAX7-FKHR fusion proteins resulting from [t(2;13)(q35;q14)] or [t(1;13)(p36;q14)] translocations, respectively. 1-3 Although a frequently affected chromosomal locus in eRMS has been defined (11p15.5), specific gene(s) or a fusion transcript have not been identified. 4 Ewing's sarcomas (EWS) and the related, more differentiated peripheral neuroectodermal tumors (PNET) are...

show abstract

In Vivo Amplification of the PAX3-FKHR and PAX7-FKHR Fusion Genes in Alveolar Rhabdomyosarcoma

Cited by 136 publications

References 21 publications

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

Allelotype of pediatric rhabdomyosarcoma

Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing's sarcoma

Contact Info

Product

Resources

About