Oncologic Phenotype of Peripheral Neuroblastic Tumors Associated With PHOX2B Non-Polyalanine Repeat Expansion Mutations.
Abstract | BACKGROUND: 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.
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Authors | Solveig Heide, Julien Masliah-Planchon, Bertrand Isidor, Anne Guimier, Damien Bodet, Carole Coze, Anne Deville, Estelle Thebault, Corinne Jeanne Pasquier, Elisabeth Cassagnau, Gaelle Pierron, Nathalie Clément, Gudrun Schleiermacher, Jeanne Amiel, Olivier Delattre, Michel Peuchmaur, Franck Bourdeaut |
Journal | Pediatric blood & cancer
(Pediatr Blood Cancer)
Vol. 63
Issue 1
Pg. 71-7
(Jan 2016)
ISSN: 1545-5017 [Electronic] United States |
PMID | 26375764
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 Wiley Periodicals, Inc. |
Chemical References |
- Homeodomain Proteins
- NBPhox protein
- Transcription Factors
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Topics |
- Adult
- Causality
- Child
- Child, Preschool
- Chromosome Aberrations
- DNA Repeat Expansion
- Ganglioneuroblastoma
(genetics, pathology)
- Ganglioneuroma
(pathology)
- Homeodomain Proteins
(genetics)
- Humans
- Hypothalamic Diseases
(genetics, pathology)
- Hypoventilation
(congenital, genetics, pathology)
- Infant
- Mutation
- Neuroblastoma
(genetics, pathology, therapy)
- Nucleic Acid Hybridization
- Peripheral Nervous System Neoplasms
(genetics, pathology, therapy)
- Phenotype
- Prognosis
- Sleep Apnea, Central
(genetics, pathology)
- Transcription Factors
(genetics)
- Treatment Outcome
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