{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:07:27Z","timestamp":1762542447563},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,9,16]],"date-time":"2015-09-16T00:00:00Z","timestamp":1442361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Association Enfance et Cancer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Germline non\u2010polyalanine repeat expansion mutations in <jats:italic>PHOX2B<\/jats:italic> (<jats:italic>PHOX2B<\/jats:italic> NPARM) predispose to peripheral neuroblastic tumors (PNT), frequently in association with other neurocristopathies: Hirschsprung disease (HSCR) or congenital central hypoventilation syndrome (CCHS). Although <jats:italic>PHOX2B<\/jats:italic> polyalanine repeat expansions predispose to a low incidence of benign PNTs, the oncologic phenotype associated with <jats:italic>PHOX2B<\/jats:italic> NPARM is still not known in detail.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed prognostic factors, treatment toxicity, and outcome of patients with PNT and <jats:italic>PHOX2B<\/jats:italic> NPARM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirteen patients were identified, six of whom also had CCHS and\/or HSCR, one also had late\u2010onset hypoventilation with hypothalamic dysfunction (LO\u2010CHS\/HD), and six had no other neurocristopathy. Four tumours were \u201cpoorly differentiated,\u201d and nine were differentiated, including five ganglioneuromas, three ganglioneuroblastomas, and one differentiating neuroblastoma, hence illustrating that <jats:italic>PHOX2B<\/jats:italic> NPARM are predominantly associated with differentiating tumors. Nevertheless, three patients had stage 4 and one patient had stage 3 disease. Segmental chromosomal alterations, correlating with poor prognosis, were found in all the six tumors analyzed by array\u2010comparative genomic hybridization. One patient died of tumor progression, one is on palliative care, one died of hypoventilation, and 10 patients are still alive, with median follow\u2010up of 5 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Based on histological phenotype, our series suggests that heterozygous <jats:italic>PHOX2B<\/jats:italic> NPARM do not fully preclude ganglion cell differentiation in tumors. However, this tumor predisposition syndrome may also be associated with poorly differentiated tumors with unfavorable genomic profiles and clinically aggressive behaviors. The intrafamilial variability and the unpredictable tumor prognosis should be considered in genetic counseling. Pediatr Blood Cancer 2015; 9999:XX\u2013XX \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.25723","type":"journal-article","created":{"date-parts":[[2015,9,16]],"date-time":"2015-09-16T13:33:48Z","timestamp":1442410428000},"page":"71-77","source":"Crossref","is-referenced-by-count":16,"title":["Oncologic Phenotype of Peripheral Neuroblastic Tumors Associated With <i>PHOX2B<\/i> Non\u2010Polyalanine Repeat Expansion Mutations"],"prefix":"10.1002","volume":"63","author":[{"given":"Solveig","family":"Heide","sequence":"first","affiliation":[{"name":"Service de Pathologie H\u00f4pital Robert Debr\u00e9, APHP Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julien","family":"Masliah\u2010Planchon","sequence":"additional","affiliation":[{"name":"INSERM U830 G\u00e9n\u00e9tique et Biologie des Cancers Institut Curie Paris France"},{"name":"Institut Curie Unit\u00e9 de G\u00e9n\u00e9tique Somatique Institut Curie Paris 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