کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2145775 1088826 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Erroneous class switching and false VDJ recombination: Molecular dissection of t(8;14)/MYC-IGH translocations in Burkitt-type lymphoblastic leukemia/B-cell lymphoma
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Erroneous class switching and false VDJ recombination: Molecular dissection of t(8;14)/MYC-IGH translocations in Burkitt-type lymphoblastic leukemia/B-cell lymphoma
چکیده انگلیسی


• Establishes an extensive map of MYC-IGH translocations with previously unmatched accuracy.
• Shows an unexpectedly high frequency of MYC translocations to the Ce switch region.
• Reveals complex MYC translocations in a switch-rearranged IGH gene locus.
• Investigates correlations between somatic hypermutation and IGH and MYC break location.
• Provides a map of the most frequently mutated amino acids in the MYC protein.

The chromosomal translocation t(8;14)(q24;q32) with juxtaposition of MYC to enhancer elements in the immunoglobulin heavy chain (IGH) gene locus is the genetic hallmark of the majority of Burkitt lymphoma and a subset of Diffuse large B-cell lymphoma patients. Around 3% of adult B-lineage acute lymphoblastic leukemia (ALL) patients show this aberration. Flow cytometry mostly reveals a “mature B-ALL” or “Burkitt-type” ALL immunophenotype. Using long-distance PCR for t(8;14)/MYC-IGH fusion, we investigated bone marrow, peripheral blood and a few other samples with suspected Burkitt-ALL or mature B-ALL and identified 133 MYC-IGH-positive cases. The location of the chromosomal breaks in the IGH joining and the 8 different switch regions was determined using a set of long-distance PCRs. The chromosomal breakpoints with the adjacent MYC regions on 8q24 were characterized by direct sequencing in 49 cases. The distribution of chromosomal breaks among the IGH joining and switch regions was the following: JH 23.3%, M 21.8%, G1 15.0%, G2 7.5%, G3 3.8%, G4 4.5%, A1 12.8%, A2 3.8%, E 7.5%. Two breakpoint clusters near MYC were delineated. There was no clear correlation between the degree of somatic hypermutation and the chromosomal break locations. Epstein Barr virus was detected in 5 cases (4%). This detailed and extensive molecular analysis illustrates the molecular complexity of the MYC-IGH translocations and the detected distribution of breakpoints provides additional evidence that this translocation results from failed switch and VDJ recombinations. This study may serve as a model for the analysis of other IGH translocations in B-cell lymphoma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 7, Issue 4, August 2013, Pages 850–858
نویسندگان
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