Molecular Localization of the t(11;22)(q24;q12) Translocation of Ewing Sarcoma by Chromosomal in situ Suppression Hybridization

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 3; pp. 887 - 891
• Main Authors: Selleri, Licia, Hermanson, Gary G., Eubanks, James H., Lewis, Kathy A., Evans, Glen A.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.02.1991; National Acad Sciences
• Subjects: 550201 - Biochemistry- Tracer Techniques; ANIMAL CELLS; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; Cell Line; Cell lines; CHROMOSOMAL ABERRATIONS; chromosome 11; chromosome 22; Chromosome Mapping; Chromosome translocation; CHROMOSOMES; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 22; COSMIDS; DAYS LIVING RADIOISOTOPES; DISEASES; Diseases of the osteoarticular system; DNA HYBRIDIZATION; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; ELECTROPHORESIS; Genes; GENETIC MAPPING; HETEROCHROMOSOMES; Humans; HYBRIDIZATION; In situ hybridization; Interphase; ISOTOPES; Karyotyping; Leukemia; LIGHT NUCLEI; MAPPING; Medical sciences; Metaphase; MUTATIONS; NEOPLASMS; NUCLEI; Nucleic Acid Hybridization; ODD-ODD NUCLEI; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; RADIOISOTOPES; Restriction Mapping; Sarcoma, Ewing - genetics; SARCOMAS; Suppression, Genetic; translocation; Translocation, Genetic; TUMOR CELLS; Tumors; Tumors of striated muscle and skeleton; Human; Translocation; Molecular hybridization; Breakpoint; Ewing sarcoma; In situ; C11-Chromosome; Diseases of the osteoarticular system; Bone; Malignant tumor; Localization; G22»-Chromosome
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.3.887

Chromosome translocations are associated with a variety of human leukemias, lymphomas, and solid tumors. To localize molecular markers flanking the t(11;22) (q24;q12) breakpoint that occurs in virtually all cases of Ewing sarcoma and peripheral neuroepithelioma, high-resolution chromosomal in situ suppression hybridization was carried out using a panel of cosmid clones localized and ordered on chromosome 11q. The location of the Ewing sarcoma translocation breakpoint was determined relative to the nearest two cosmid markers on 11q, clones 23.2 and 5.8, through the analysis of metaphase chromosome hybridization. By in situ hybridization to interphase nuclei, the approximate physical separation of these two markers was determined. In both Ewing sarcoma and peripheral neuroepithelioma, cosmid clone 5.8 is translocated from chromosome 11q24 to the derivative chromosome 22 and a portion of chromosome 22q12 carrying the leukemia inhibitory factor gene is translocated to the derivative chromosome 11. The physical distance between the flanking cosmid markers on chromosome 11 was determined to be in the range of 1000 kilobases, and genomic analysis using pulsed-field gel electrophoresis showed no abnormalities over a region of 650 kilobases in the vicinity of the leukemia inhibitory factor gene on chromosome 22. This approach localizes the Ewing sarcoma breakpoint to a small region on chromosome 11q24 and provides a rapid and precise technique for the molecular characterization of chromosomal aberrations.