In:
Pediatric Blood & Cancer, Wiley, Vol. 63, No. 1 ( 2016-01), p. 71-77
Abstract:
Germline non‐polyalanine repeat expansion mutations in PHOX2B ( PHOX2B NPARM) predispose to peripheral neuroblastic tumors (PNT), frequently in association with other neurocristopathies: Hirschsprung disease (HSCR) or congenital central hypoventilation syndrome (CCHS). Although PHOX2B polyalanine repeat expansions predispose to a low incidence of benign PNTs, the oncologic phenotype associated with PHOX2B NPARM is still not known in detail. Methods We analyzed prognostic factors, treatment toxicity, and outcome of patients with PNT and PHOX2B NPARM. Results Thirteen patients were identified, six of whom also had CCHS and/or HSCR, one also had late‐onset hypoventilation with hypothalamic dysfunction (LO‐CHS/HD), and six had no other neurocristopathy. Four tumours were “poorly differentiated,” and nine were differentiated, including five ganglioneuromas, three ganglioneuroblastomas, and one differentiating neuroblastoma, hence illustrating that PHOX2B 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‐comparative 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‐up of 5 years. Conclusions Based on histological phenotype, our series suggests that heterozygous PHOX2B 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–XX © 2015 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
1545-5009
,
1545-5017
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2130978-4
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