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Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1.

Publication ,  Journal Article
McPherson, JR; Ong, C-K; Ng, CC-Y; Rajasegaran, V; Heng, H-L; Yu, WS-S; Tan, BK-T; Madhukumar, P; Teo, MC-C; Ngeow, J; Thike, A-A; Rozen, SG ...
Published in: Cancer Med
December 2015

Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by the development of multiple neurofibromas, cafe-au-lait spots, and Lisch nodules. Individuals with NF1 are at increased risk of developing various tumors, such as malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, leukemia, glioma, rhabdomyosarcoma, and breast cancer. Here, we describe the exome sequencing of breast cancer, MPNST, and neurofibroma from a patient with NF1. We identified a germline mutation in the NF1 gene which resulted in conversion of leucine to proline at amino acid position 847. In addition, we showed independent somatic NF1 mutations in all the three tumors (frameshift insertion in breast cancer (p.A985fs), missense mutation in MPNST (p.G23R), and inframe deletion in dermal neurofibroma (p.L1876del-Inf)), indicating that a second hit in NF1 resulting in the loss of function could be important for tumor formation. Each tumor had a distinct genomic profile with mutually exclusive mutations in different genes. Copy number analysis revealed multiple copy number alterations in the breast cancer and the MPNST, but not the benign neurofibroma. Germline loss of chromosome 6q22.33, which harbors two potential tumor suppressor genes, PTPRK and LAMA2, was also identified; this may increase tumor predisposition further. In the background of NF1 syndrome, although second-hit NF1 mutation is critical in tumorigenesis, different additional mutations are required to drive the formation of different tumors.

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Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

December 2015

Volume

4

Issue

12

Start / End Page

1871 / 1878

Location

United States

Related Subject Headings

  • Neurofibromin 1
  • Neurofibromatosis 1
  • Neurofibroma
  • Nerve Sheath Neoplasms
  • Neoplasms, Multiple Primary
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Germ-Line Mutation
  • Female
  • Exome
 

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McPherson, J. R., Ong, C.-K., Ng, C.-Y., Rajasegaran, V., Heng, H.-L., Yu, W.-S., … Yap, Y.-S. (2015). Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1. Cancer Med, 4(12), 1871–1878. https://doi.org/10.1002/cam4.551
McPherson, John Richard, Choon-Kiat Ong, Cedric Chuan-Young Ng, Vikneswari Rajasegaran, Hong-Lee Heng, Willie Shun-Shing Yu, Benita Kiat-Tee Tan, et al. “Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1.Cancer Med 4, no. 12 (December 2015): 1871–78. https://doi.org/10.1002/cam4.551.
McPherson JR, Ong C-K, Ng CC-Y, Rajasegaran V, Heng H-L, Yu WS-S, et al. Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1. Cancer Med. 2015 Dec;4(12):1871–8.
McPherson, John Richard, et al. “Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1.Cancer Med, vol. 4, no. 12, Dec. 2015, pp. 1871–78. Pubmed, doi:10.1002/cam4.551.
McPherson JR, Ong C-K, Ng CC-Y, Rajasegaran V, Heng H-L, Yu WS-S, Tan BK-T, Madhukumar P, Teo MC-C, Ngeow J, Thike A-A, Rozen SG, Tan P-H, Lee AS-G, Teh B-T, Yap Y-S. Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1. Cancer Med. 2015 Dec;4(12):1871–1878.
Journal cover image

Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

December 2015

Volume

4

Issue

12

Start / End Page

1871 / 1878

Location

United States

Related Subject Headings

  • Neurofibromin 1
  • Neurofibromatosis 1
  • Neurofibroma
  • Nerve Sheath Neoplasms
  • Neoplasms, Multiple Primary
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Germ-Line Mutation
  • Female
  • Exome