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2.5 The case of Burkitt’s lymphoma

Careful examination of metaphase chromosome spreads of these tumor cells did revealed the tumor cells almost invariably carried chromosomal translocations Such alterations fuse a region from one chromosome with another region from a second, unrelated chromosome Chromosomal Translocations Translocations such as these are often found to be reciprocal. The chromosomal region from chromosome A lands on chromosome B, the displaced segment of chromosome B ends up being linked to chromosome A. Chromosomal Translocations Burkitt’s lymphoma In the case of Burkitt’s lymphomas, three distinct, alternative chromosomal translocations were found, involving human Chromosomes 2, 14, or 22. The three translocations were united by the fact that in each case, a region from one of these three chromosomes was fused to a section of Chromosome 8. What is it about Chromosome 8? The myc proto-oncogene could be found in the region on human Chromosome 8 that is involved in these translocations. On the other side of the fusion site (often termed the chromosomal breakpoint) were found the transcription-promoting sequences from any one of three distinct immunoglobulin (antibody) genes. the immunoglobulin heavy-chain gene cluster is found on Chromosome 14 the K antibody light-chain gene is located on Chromosome 2 the 2 antibody light-chain gene is found on Chromosome 22 Translocations separate myc from its promoter The enzymes responsible for rearranging the sequences of antibody genes inadvertently fuse part of an antibody gene with the myc proto-oncogene. These translocations separate the myc gene from its normal transcriptional promoter and place it under the control of one of three highly active transcriptional regulators each from an immunoglobulin gene Many distinct chromosomal translocations have been found to cause deregulated expression of known proto-oncogenes Most of these genes remain poorly characterized