PHOX2B

Paired-like homeobox 2b (PHOX2B), also known as neuroblastoma Phox (NBPhox), is a protein that in humans is encoded by the PHOX2B gene located on chromosome 4.[5]

PHOX2B
Identifiers
AliasesPHOX2B, NBLST2, NBPhox, PMX2B, paired like homeobox 2b, CCHS
External IDsOMIM: 603851 MGI: 1100882 HomoloGene: 68371 GeneCards: PHOX2B
Gene location (Human)
Chr.Chromosome 4 (human)[1]
Band4p13Start41,744,082 bp[1]
End41,748,725 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

8929

18935

Ensembl

ENSG00000109132

ENSMUSG00000012520

UniProt

Q99453

O35690

RefSeq (mRNA)

NM_003924

NM_008888

RefSeq (protein)

NP_003915

NP_032914

Location (UCSC)Chr 4: 41.74 – 41.75 MbChr 5: 67.09 – 67.1 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

It codes for a homeodomain transcription factor. It is expressed exclusively in the nervous system, in most neurons that control the viscera (cardiovascular, digestive and respiratory systems). It is also required for their differentiation.

Immunohistochemistry

Essential for the differentiation and survival of sympathetic neurons and chromaffin cells, the transcription factor PHOX2B is highly specific for the peripheral autonomic nervous system. Neuroblasts are derived from sympathoadrenal lineage neural crest cells and therefore require and constitutively express PHOX2B. PHOX2B immunohistochemical staining, as a marker of neural crest derivation, has been shown to be sensitive and specific for undifferentiated neuroblastoma, enabling identification where other markers fail to recognize neuroblastoma among various different small round blue cell tumors of childhood.[6][7][8][9]

The diagnostic utility of PHOX2B staining extends to later stages of differentiation. Its strength and specificity can detect the small foci of neuroblastic tumors metastatic to the bone marrow, an identification critical for determining disease staging. PHOX2B staining also overcomes frequent obstacles to neuroblastoma detection in post-treatment samples, which frequently exhibit dense fibrosis, prominent inflammatory infiltrates, and/or diffuse calcification.[10]

Pathology

Mutations in human PHOX2B cause a rare disease of the visceral nervous system (dysautonomia): congenital central hypoventilation syndrome (associated with respiratory arrests during sleep and, occasionally, wakefulness), Hirschsprung's disease (partial agenesis of the enteric nervous system), ROHHAD, and tumours of the sympathetic ganglia. In most people, Exon 3 of the gene contains a sequence of 20 polyalanine repeats. An increase in the number of repeats is associated with congenital central hypoventilation syndrome. There may also be other pathogenic mutations further along the gene.

References

  1. GRCh38: Ensembl release 89: ENSG00000109132 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000012520 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: paired-like homeobox 2b".
  6. Bielle, Franck; Fréneaux, Paul; Jeanne-Pasquier, Corinne; Maran-Gonzalez, Aurélie; Rousseau, Audrey; Lamant, Laurence; Paris, Régine; Pierron, Gaëlle; Nicolas, André Victor; Sastre-Garau, Xavier; Delattre, Olivier; Bourdeaut, Franck; Peuchmaur, Michel (2012). "PHOX2B Immunolabeling". The American Journal of Surgical Pathology. 36 (8): 1141–1149. doi:10.1097/PAS.0b013e31825a6895. PMID 22790854. S2CID 25924210.
  7. Hata, Jessica L.; Correa, Hernan; Krishnan, Chandra; Esbenshade, Adam J.; Black, Jennifer O.; Chung, Dai H.; Mobley, Bret C. (2015). "Diagnostic Utility of PHOX2B in Primary and Treated Neuroblastoma and in Neuroblastoma Metastatic to the Bone Marrow". Archives of Pathology & Laboratory Medicine. 139 (4): 543–546. doi:10.5858/arpa.2014-0255-OA. PMID 25822764.
  8. Hung, Yin P.; Lee, John P.; Bellizzi, Andrew M.; Hornick, Jason L. (2017). "PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours". Histopathology. 71 (5): 786–794. doi:10.1111/his.13288. PMID 28640941. S2CID 19123236.
  9. Warren, Mikako; Matsuno, Ryosuke; Tran, Henry; Shimada, Hiroyuki (2018). "Utility of Phox2b immunohistochemical stain in neural crest tumours and non-neural crest tumours in paediatric patients". Histopathology. 72 (4): 685–696. doi:10.1111/his.13412. PMID 28986989. S2CID 3302863.
  10. Hata et al. (2015).

Further reading


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.