التفاصيل البيبلوغرافية
| العنوان: |
Human Chromosomal Translocations at CpG Sites and a Theoretical Basis for Their Lineage and Stage Specificity |
| المؤلفون: |
Tsai, Albert G.1, Lu, Haihui1, Raghavan, Sathees C.1, Muschen, Markus2, Hsieh, Chih-Lin1, Lieber, Michael R.1 lieber@usc.edu |
| المصدر: |
Cell. Dec2008, Vol. 135 Issue 6, p1130-1142. 13p. |
| مصطلحات موضوعية: |
*CHROMOSOMAL rearrangement, *PROTEINS, *LYMPHOMAS, *GENE amplification, *DOUBLE-stranded RNA, *CHRONIC leukemia |
| مستخلص: |
Summary: We have assembled, annotated, and analyzed a database of over 1700 breakpoints from the most common chromosomal rearrangements in human leukemias and lymphomas. Using this database, we show that although the CpG dinucleotide constitutes only 1% of the human genome, it accounts for 40%–70% of breakpoints at pro-B/pre-B stage translocation regions—specifically, those near the bcl-2, bcl-1, and E2A genes. We do not observe CpG hotspots in rearrangements involving lymphoid-myeloid progenitors, mature B cells, or T cells. The stage specificity, lineage specificity, CpG targeting, and unique breakpoint distributions at these cluster regions may be explained by a lesion-specific double-strand breakage mechanism involving the RAG complex acting at AID-deaminated methyl-CpGs. [Copyright &y& Elsevier] |
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