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Jonathan A Fletcher

Publications and source records attributed to Jonathan A Fletcher.

58 records · Page 4Linked to original sources
PubMedDate not supplied

Peripheral nerve sheath tumors from patients with neurofibromatosis type 1 do not have the chromosomal translocation t(X;18).

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder that is caused by a mutation in the NF1 gene. Hallmark characteristics include dermal neurofibromas, café-au-lait spots, and learning disabilities. In approximately 25% of NF1 cases, plexiform neurofibromas, or peripheral nerve sheath tumors (PNSTs) that involve large segments of nerve sheath and nerve root, can form, of which a small percentage become malignant (MPNST). Most MPNSTs are composed of spindled neoplastic cells, and they can resemble other spindle-cell sarcomas, including leiomyosarcoma and monophasic synovial sarcoma. Histological diagnosis of MPNST is not always straightforward, and various immunohistochemical and molecular adjuncts can be critical in establishing a correct diagnosis. One example of genetic testing is the assay for the t(X;18) chromosomal translocation, which has been found to be common in synovial sarcomas. The aim of this study was to determine whether MPNSTs contain the t(X;18) chromosomal translocation. To detect the t(X;18) translocation product, SYT-SSX, total RNA was extracted from frozen archival tumors (15 dermal neurofibromas, 4 plexiform neurofibromas, and 7 MPNSTs) using Trizol. The RNA was then subjected to reverse-transcriptase polymerase chain reaction (RT-PCR) to specifically amplify SYT-SSX. None of the dermal neurofibromas, plexiform neurofibromas, or MPNSTs analyzed were positive for SYT-SSX mRNA. The results indicate that the t(X;18) translocation is absent in neurofibromas and is not a marker for MPNST in patients with NF1.

Biomarkers, Tumor↗
PubMedDate not supplied

Cytogenetic and p53 profiles in congenital cystic adenomatoid malformation: insights into its relationship with pleuropulmonary blastoma.

Congenital cystic adenomatoid malformation (CCAM), a developmental anomaly of lung, shares many features with the pediatric tumor pleuropulmonary blastoma (PPB). Both may show benign epithelium-lined cysts and mesenchymal proliferation, often with skeletal muscle differentiation. Before its recognition as a distinct entity, PPB was described in several reports as "rhabdomyosarcoma arising in CCAM." Abnormal karyotypes in PPB often show excess material from chromosome 8. It has also been suggested that PPB may harbor p53 mutations. We examined the karyotype and searched for p53 mutations (via immunostaining and single-strand conformation polymorphism analysis) in 11 CCAM and in 2 PPB. Karyotypes were normal in all CCAM and showed clonal abnormalities in both PPB. There was marked and diffuse immunopositivity for nuclear p53 in the epithelial cells of CCAM and PPB. Strong staining was also observed in approximately 50% of the stromal cells in all PPB, but was seen in the stroma of only 2 of 10 CCAM, where it was faint and focal. TP53 mutations were not identified in CCAM or PPB. We conclude that CCAM does not contain the clonal chromosomal aberrations reported in PPB and shows less stromal p53 immunostaining than PPB. Since p53 mutations were not identified in either entity, the observed p53 immunoreactivity may be caused by another mechanism; its role in PPB and CCAM pathogenesis remains to be determined. Overall, these findings provide evidence that CCAM is nonneoplastic. Although some may view CCAM as a PPB precursor, it remains biologically distinct in terms of karyotype and p53 status.

Child, Preschool↗