Genetic Factors that Affect Tumorigenesis in NF1
Abstract
Neurofibromatosis type 1 affects 1/4000 individuals worldwide and predisposes to the growth of both benign and malignant tumors. Our research is focused on NFl microdeletions that are associated with an early onset, and subsequent heavy burden, of cutaneous neurofibromas. We reported that the deletions arise by homologous recombination between 51 kb repeat elements (NR1REP) that flank the NF1 gene. We identified recombination hotspots where 69% of NF1 microdeletions occur and developed robust and sensitive assays to detect microdeletions in a patient blood sample. We analyzed the structure and sequence of four NR1REP paralogs in the genome and described sequence features that may mediate recombination at these sites. We developed new quantitative PCR assays that will detect nonrecurrent NFl microdeletions that occur either in the germline or in somatic tissues including tumors. Our data make substantial contributions to understanding how NFl microdeletions occur, create resources to inquire whether some individuals are more susceptible, and which deleted sequences may cause the severe tumor phenotype of these patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2003
- Accession Number
- ADA425539
Entities
People
- Karen Stephens
Organizations
- University of Washington