Genetic Predisposition to Neuroblastoma
Abstract
:1. Introduction
2. Familial Neuroblastoma
2.1. PHOX2B
2.2. ALK
2.3. KIF1Bβ
2.4. RAS Pathway Mutations and Other Cancer Predisposition Syndromes
2.5. Other Predisposition Syndromes
3. Sporadic Neuroblastoma
3.1. Susceptibility to Sporadic Neuroblastoma
3.2. Predisposition to Neuroblastoma Genotypes
4. Future Directions
4.1. Germline Genetics Predisposing to Adverse Events
4.2. Beyond Caucasians in Sporadic Neuroblastoma
4.3. Collaboration with Therapeutic and Technological Advances
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Syndrome/Disease | Gene | Typical Genetic Alterations | Clinical Findings | Pre-Disposed Tumors |
---|---|---|---|---|
Congenital Central Hypoventilation Syndrome (CCHS) [32,33,36] | PHOX2B | Polyalanine and nonpolyalanine repeat expansion (frameshift or missense) | Respiratory dysfunction, autonomic dysfunction, Hirschsprung disease, neural crest tumors | Neuroblastoma, ganglioneuroma, ganglioneuroblastoma |
ROHHAD [64,65,66,67] | Unknown | Unknown | Autonomic dysfunction, endocrinopathies, alveolar hypoventilation | Neuroblastoma, ganglioneuroma, ganglioneuroblastoma |
Costello [58,59,60] | HRAS | Activating missense | Intellectual disability, coarse facial features, loose folds of skin, heart abnormalities, joint flexibility | Papilloma, rhabdomyosarcoma, neuroblastoma, transitional cell carcinoma |
Noonan [52,53,54,60] | PTPN11, SOS1, RAF1, KRAS | Activating | Short stature, heat abnormalities, skeletal abnormalities, bleeding | Leukemia, neuroblastoma |
Neurofibromatosis type 1 [55,56,57,60] | NF1 | Activating | Abnormal skin pigmentation, neurofibromas, scoliosis | Neurofibroma, MPNST, brain tumors, leukemia, optic glioma, neuroblastoma |
Beckwith–Wiedemann [68,69,70,71] | CDKN1C *, H19, IGF2, KNBQOT1 | Abnormal methylation of chromosome 11 or uniparental disomy | Macrosomia, hemihypertrophy, abdominal wall defects, visceromegaly | Wilms tumor, hepatoblastoma, neuroblastoma |
Li–Fraumeni [51,62,63] | TP53 | Missense | Increased cancer risk | Breast cancer, osteosarcoma, brain tumors, leukemia, neuroblastoma, adrenocortical carcinoma, soft tissue sarcoma |
Weaver Syndrome [72] | EZH2 | Missense and truncating | Tall stature, intellectual disability, joint deformities, hypertelorism, micrognathia | Neuroblastoma |
Familial Paraganglioma/Pheochromocytoma [73,74] | SDHB *, SDHAF2, SDHC, SDHD | Splice site, frameshift, nonsense | Growth of benign tumors in paraganglia | Paraganglioma, pheochromocytoma, neuroblastoma |
Fanconi Anemia [75,76,77,78,79] | FANCA, FANCC, FANCG, BRCA1, BRCA2 *, PALB2 *, BRIP1 *, and many others | Truncating, frameshift, missense | Bone marrow failure, organ defects, skeletal abnormalities | Leukemia, Wilms tumor, medulloblastoma, neuroblastoma, embryonal tumors, sarcomas, nephroblastoma |
Candidate Gene(s) | Variant * | Genomic Location |
---|---|---|
TP53 [63] | rs35850753 | 17p13.1 |
CASC-15 and NBAT-1 [84] | rs6939340 | 6p22 |
BARD1 [88] | rs6435862 | 2q35 |
LMO1 [96] | rs2168101 | 11p15.4 |
DUSP12 [100] | rs1027702 | 1q23.3 |
DDX4 [100] | rs2619046 | 5q11.2 |
IL31RA [100] | rs10055201 | 5q11.2 |
HSD17B12 [100] | rs11037575 | 11p11.2 |
HACE1 [101] | rs4336470 | 6q16 |
LIN28B [101] | rs17065417 | 6q16 |
CPZ [106] | rs3796727 | 4p16 |
MLF1 [106] | rs6441201 | 3q25 |
NEFL [108] | rs1059111 | 8q21 |
CDKN1B [109] | rs34330 | 12p13 |
KIF15 [113] | rs80059929 | 3p21.31 |
MMP20 [116] | rs10895322 | 11q22.2 |
SPAG16 [117] | rs1033069 | 2q34 |
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Barr, E.K.; Applebaum, M.A. Genetic Predisposition to Neuroblastoma. Children 2018, 5, 119. https://doi.org/10.3390/children5090119
Barr EK, Applebaum MA. Genetic Predisposition to Neuroblastoma. Children. 2018; 5(9):119. https://doi.org/10.3390/children5090119
Chicago/Turabian StyleBarr, Erin K., and Mark A. Applebaum. 2018. "Genetic Predisposition to Neuroblastoma" Children 5, no. 9: 119. https://doi.org/10.3390/children5090119