Neurofibromatosis Type I (NF1) is an autosomal dominant disorder characterized by the development of both benign and malignant tumors. The lifetime risk for developing a malignant peripheral nerve sheath tumor (MPNST) in NF1 patients is approximately 10% with poor survival rates.
Types
NF1-associated neurofibroma
NF1-associated malignant peripheral nerve sheath tumor (MPNST)
CGH (19603524)
losses
- 1p35-33 loss
- 1p21 loss
- 9p21.3 loss
- 10q25 loss
- 11q22-23 loss
- 17q11 loss
- 20p12.2 loss
gains
- 1q25
- 3p26
- 3q13
- 5p12
- 5q11.2-q14
- 5q21-23
- 5q31-33
- 6p23-p21
- 6p12
- 6q15
- 6q23-q24
- 7p22
- 7p14-p13
- 7q21, 7q36
- 8q22-q24
- 14q22
- 17q21-q25
Copy number gains are more frequent than deletions in the MPNST samples (62% vs. 38%). The genes resident within common regions of gain were NEDL1 (7p14), AP3B1 (5q14.1), and CUL1 (7q36.1) and these are identified in >63% MPNSTs. (19603524)
The most frequently deleted locus encompassed CDKN2A, CDKN2B, and MTAP genes on 9p21.3 (33% cases). (19603524)
These genes have previously been implicated in other cancer conditions and therefore, should be considered for their therapeutic, prognostic, and diagnostic relevance in NF1 tumorigenesis. (19603524)
References
Genome-wide high-resolution analysis of DNA copy number alterations in NF1-associated malignant peripheral nerve sheath tumors using 32K BAC array. Mantripragada KK, de Ståhl TD, Patridge C, Menzel U, Andersson R, Chuzhanova N, Kluwe L, Guha A, Mautner V, Dumanski JP, Upadhyaya M. Genes Chromosomes Cancer. 2009 Oct;48(10):897-907. PMID: 19603524