title: Interphase fluorescence in situ hybridization for detection of 8q24/MYC breakpoints on routine histologic sections: validation in Burkitt lymphomas from three geographic regions.
abstract: A chromosomal translocation involving the MYC gene is characteristic of Burkitt lymphoma (BL) and represents a molecular disease marker with diagnostic and clinical implications. The detection of MYC breakpoints is hampered by technical problems, including the distribution of the breakpoints over a very large genomic region of approximately 1,000 kb. In this article, we report on the testing and validation of a segregation fluorescence in situ hybridization (FISH) assay for MYC breakpoints on a large series of BLs. A contig of overlapping genomic clones was generated, and two probe sets flanking the MYC gene were selected. Both probe sets were tested in an interphase FISH segregation assay on 8 B-cell lymphoma cell lines and 32 lymphoma samples with proved 8q24/MYC abnormalities and validated in 47 BLs from The Netherlands, Brazil, and Uganda. MYC translocation breakpoints were identified in 98% of the tumors of the test series and in 89% of the cases of the validation series. In 89% of all positive samples, the breakpoints were located between 190 kb 5' and 50 kb 3' of MYC. Nine cases had more distant breakpoints, and in one patient an insertion of MYC into the IGH region was detected. In two of the three BLs lacking CD10 expression, no breakpoint could be detected, suggesting that CD10 is a discriminative marker of BL. We did not find consistent differences between BL and atypical BL in incidence of an MYC breakpoint.
authors.affiliation: Department of Pathology & Laboratory Medicine, University Hospital Groningen, Groningen, The Netherlands.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Haralambieva
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.forename: Stefano
authors.initials: S
authors.lastname: Rosati
authors.forename: Carel
authors.initials: C
authors.lastname: van Noesel
authors.forename: Patty
authors.initials: P
authors.lastname: Jansen
authors.forename: Inge
authors.initials: I
authors.lastname: Appel
authors.forename: Jeroen
authors.initials: J
authors.lastname: Guikema
authors.forename: Henry
authors.initials: H
authors.lastname: Wabinga
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Bleggi-Torres
authors.forename: King
authors.initials: K
authors.lastname: Lam
authors.forename: Eva
authors.initials: E
authors.lastname: van den Berg
authors.forename: Clemens
authors.initials: C
authors.lastname: Mellink
authors.forename: Shama
authors.initials: S
authors.lastname: van Zelderen-Bhola
authors.forename: Philip
authors.initials: P
authors.lastname: Kluin
mesh_terms: D000293:Adolescent; D000328:Adult; D002051:Burkitt Lymphoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D015342:DNA Probes / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007399:Interphase / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000378:metabolism; D008875:Middle Aged
chemical_list: D015342:DNA Probes; D004273:DNA, Neoplasm; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase