MIM.136533 13q14.1 HGNC.3819
Friday 2 February 2007
PAX3/FOXOA1 or PAX7/FOXOA1 fusion genes in alveolar rhabdomyosarcoma
- Alveolar rhabdomyosarcoma (ARMS) is an aggressive neoplasm with unique t(2;13)(q35;q14) or t(1;13)(p36;q14) chromosomal translocations, resulting in PAX3/FOXO1 and PAX7/FOXO1 fusion genes, in approximately 80% of cases.
- These translocations and their gene fusions have not been identified in other neoplasms, making their identification an attractive target for applying ancillary diagnostic techniques such as fluorescence in situ hybridization (FISH).
FOXOA1 deletion in cancer
- Deletion at FOXO1A was detected in 31% to 34% in 6 cell lines, 27 xenografts, and 72 clinical specimens of prostate cancer, and was significantly more frequent than deletions at surrounding loci. (16849544)
down-regulation of FOXOA1
- FOXO1A was transcriptionally down-regulated in some prostate cancers. Functionally, ectopic expression of FOXO1A inhibited, and its knockdown promoted, cell proliferation or survival. (16849544)
- FOXO1A inhibited androgen- and androgen receptor-mediated gene regulation and cell proliferation. (16849544)
- FOXO1A is the 13q14 tumor suppressor gene, at least in prostate cancer. (16849544)
- As a well-established negative effector in the phosphatidylinositol 3-kinase/AKT signaling pathway, FOXO1A inactivation in cancer would impair the therapeutic effect of phosphatidylinositol 3-kinase/AKT inhibitors in cancer treatment. (16849544)
FOXO1 (13q14) FISH
FOXO1 (13q14) FISH on formalin-fixed, paraffin-embedded tissues samples showed excellent concordance with reverse transcription polymerase chain reaction and cytogenetic analyses in ARMS cases, demonstrated excellent specificity (100%) when applied to potential mimickers such as EWS/PNET, and played an important role in the differential diagnosis of small round cell tumors.
The utility of FOXO1 fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded specimens in the diagnosis of alveolar rhabdomyosarcoma. Downs-Kelly E, Shehata BM, López-Terrada D, Weaver J, Patel RM, Hartke M, Tubbs RR, Skacel M, Goldblum JR. Diagn Mol Pathol. 2009 Sep;18(3):138-43. PMID: 19704258
Kim JH, Kim MK, Lee HE, Cho SJ, Cho YJ, Lee BL, Lee HS, Nam SY, Lee JS, Kim WH. Constitutive phosphorylation of the FOXO1A transcription factor as a prognostic variable in gastric cancer. Mod Pathol. 2007 Aug;20(8):835-42. PMID: 17491598
Dong XY, Chen C, Sun X, Guo P, Vessella RL, Wang RX, Chung LW, Zhou W, Dong JT. FOXO1A is a candidate for the 13q14 tumor suppressor gene inhibiting androgen receptor signaling in prostate cancer. Cancer Res. 2006 Jul 15;66(14):6998-7006. PMID: 16849544
Barr FG. Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma. Oncogene. 2001 Sep 10;20(40):5736-46. PMID: 11607823
Barr, F. G.; Galili, N.; Holick, J.; Biegel, J. A.; Rovera, G.; Emanuel, B. S. Rearrangement of the PAX3 paired box gene in the paediatric solid tumor alveolar rhabdomyosarcoma. Nature Genet. 3: 113-117, 1993. PubMed ID : 8098985