Elizabeth F. Allen

Genetic Characterization of Angiomatoid Fibrous Histiocytoma Identifies Fusion of the FUS and ATF-1 Genes Induced by a Chromosomal Translocation Involving Bands 12q13 and 16p11

This case report documents the first karyotypic, fluorescence in situ hybridization, and genetic analysis of an angiomatoid fibrous histiocytoma that arose and recurred in the arm of a 5.5-year-old girl. Complex rearrangements between chromosomes 2, 12, 16, and 17 were noted, as well as deletion in the long arm of chromosome 11. Flow cytometry revealed a normal cell population. The t(12;16) site was further investigated using reverse transcriptase-polymerase chain reaction. We found that the FUS (also known as TLS) gene from 16p11 combined with the ATF-1 gene from 12q13 to generate a chimeric FUS/ATF-1. The FUS gene is rearranged in the t(12;16)(q13;p11) that characterizes myxoid liposarcoma and in acute myeloid leukemia with t(16;21)(p11;q22), while the ATF-1 gene is rearranged in the t(12;22)(q13;q12) found recurrently in clear cell sarcomas (malignant melanoma of soft parts). Thus, the FUS/ATF-1 gene in angiomatoid fibrous histiocytoma is predicted to code for a protein that is very similar to the chimeric EWS/ATF-1 found in clear cell sarcoma.

An enumerative assay of purine analogue resistant lymphocytes in women heterozygous for the Lesch-Nyhan mutation

In females heterozygous for the Lesch-Nyhan (LN) mutation, there is mosaicism of peripheral blood lymphocytes (PBLs) with regard to sensitivity to 6-thioguanine (TG) inhibition of tritiated thymidine ([3H]Tdr) incorporation following phytohemagglutinin (PHA) stimulation. That there are two populations of PBLs, normal and mutant (LN-like), has been demonstrated by an autoradiographic enumerative assay. A single three-generation family containing six potentially heterozygous females was studied. Five of the six were mosaics with frequencies of TG-resistant (TGr) PBLs ranging from 1.4×10−3 to 4.2×10−3 when tested at 2×10−4m TG. The median frequency of TGr PBLs in 63 healthy non-LN individuals between the ages of 11 and 75 years was found to be 1.1×10−4 (mean 1.3×10−4) (10th and 90th percentiles—6.1×10−5 and 2.1×10−4) and was not age related. The sixth potentially heterozygous female in the current family had a TGr PBL frequency of 1.9×10−4. In the five females with elevated TGr PBL frequencies, TGr skin fibroblasts with frequencies ranging from 26% to 100% of the sample tested were found; in the female with the normal TGr PBL frequency, no TGr skin fibroblasts were found. The former group was considered to be LN heterozygous. Four of the five had been previously diagnosed as such. The latter individual is considered to be genotypically normal. Females who are heterozygotes for the LN mutation have two populations of PBLs.

Desmoplastic small round cell tumour of unknown primary origin with lymph node and lung metastases: histological, cytological, ultrastructural, cytogenetic and molecular findings

Abstract Desmoplastic small round cell tumour (DSRCT) is an extremely aggressive neoplasm belonging to the family of ”small round blue cell tumours”, which includes primitive neuroectodermal tumour (PNET), Wilms’ tumour and Ewing’s sarcoma. DSRCT is considered to be a neoplasm derived from a primitive cell. It is immunohistochemically reactive with epithelial, neuronal and mesenchymal cell markers, demonstrating divergent differentiation along three cell lines. Originally thought to arise from serosal surfaces, the tumour has recently been reported in the central nervous system and ovary. The tumour in this case is a neoplasm that meets the histological, immunohistochemical, cytological and cytogenetic criteria of DSRCT; it is not associated with serosal membranes, and it has supraclavicular and axillary lymph node deposits and multiple pulmonary and brain metastases. Tumour cells from our case show cytogenetic similarities with Ewing’s sarcoma and PNET. Electron microscopic findings suggest similarities between DSRCT and Wilms’ tumour. Cloning and sequencing of PCR products showed in-frame fusion of EWS exon 7 to WT1 exon 8.

A case of acute myelofibrosis with complex karyotypic changes: A type of myelodysplastic syndrome

A 73-year-old woman developed a rapidly fatal disease that fit the clinical criteria for acute myelofibrosis. Over a 9 month period she progressed from normal peripheral blood counts to severe pancytopenia and finally a terminal phase with monocytosis and circulating myeloblasts. Morphologic examination of her bone marrow at presentation showed trilineage dysplasia, hypercellularity, and diffuse fibrosis with foci of immature precursors. Cytogenetic, analysis showed the karyotype 45-46, XX,del(5)(q33),+11,add(17)(q25),-18,-20,+22. The morphologic and cytogenetic findings in this case support a relationship between acute myelofibrosis and myelodysplastic syndromes. Acute myelofibrosis with complex chromosomal aberrations may represent one pathway of evolution in myelodysplasia that is associated with a particularly poor prognosis.

Interstitial 9q- deletion in a case of acute myeloid leukemia-M2 arising from a granulocytic sarcoma

Deletion of a portion of the long arm of chromosome 9, as the sole abnormality, has previously been reported in detail in 14 cases of acute myeloid leukemia (AML). We report on the first case of AML-M2 arising from granulocytic sarcoma with this chromosome abnormality as the sole karyotypic abnormality.

Mutation In Vivo in Human Somatic Cells: Studies Using Peripheral Blood Mononuclear Cells

We review here our efforts to develop a direct mutagenicity test system for detecting somatic cell mutations occurring in vivo in man. Our specific goal is to provide a useful test for directly quantifying mutant cells in human blood samples.