Germline and somatic NF1 gene mutation spectrum in NF1‐associated malignant peripheral nerve sheath tumors (MPNSTs)

摘要: About 10% of neurofibromatosis type 1 (NF1) patients develop malignant peripheral nerve sheath tumors (MPNSTs) and represent considerable patient morbidity mortality. Elucidation the genetic mechanisms by which inherited acquired NF1 disease gene variants lead to MPNST development is important. A study was undertaken identify constitutional somatic mutations in 34 MPNSTs from 27 patients. The germline identified 22 lymphocytes DNA these included seven novel a large 1.4-Mb deletion. mutation spectrum similar that previously adult without MPNST. Somatic were tumor 31 out MPNSTs, 28 genomic deletions. high prevalence (>90%) such deletions contrast with =or<20% found benign neurofibromas indicative involvement different mutational tumors. Coinactivation TP53 deletion, or point along inactivation, known exacerbate symptoms NF1, therefore inactivation screened. 20 showed evidence for loss heterozygosity (LOH) across region 11 samples, four