Researchers identify how key mutations occur in human lymphomas



Human Pheromone Sciences, Inc. has announced that it has filed a Comprehensive Patent Application with the International Bureau of the World Patent Office for the use of its innovative and previously undeveloped compound with its origin in sea coral, which has significant emotional impacts on both men and women, enhancing feelings of positive social relationships,

Full Post: HPS files world patent for mood-enhancing compound from sea coral

Researchers at the Keck School of Medicine of the University of Southern California (USC) have explained how certain key mutations occur in human lymphomas - a process that has, until now, remained a mystery.

The findings of the study, published in the Dec. 12 issue of the journal Cell, will have a significant impact on future study of how human lymphoma occurs.

Chromosomal translocations, in which segments of DNA are moved around the genome, are DNA mutations frequently found in blood cancers. They occur when two chromosomes break and the resulting fragments are reassembled in an exchange, says Michael R. Lieber, M.D/Ph.D., Rita and Edward Polusky Professor in Basic Cancer Research at the Keck School of Medicine and the study’s principal investigator.

“Our study provides new insight into understanding how these translocations occur and describes a key and informative fingerprint at these chromosomal break sites,” Lieber says.

The fingerprint had been overlooked for decades because chromosomal break sites typically suffer damage that obscures the fingerprint, he says.

“The precise steps leading to this pathologic rearrangement process - especially how the DNA is broken - have been a mystery for 25 years, in large part because these events occur long before the cancer becomes clinically apparent, and conventional experimental techniques do not reflect the process as it occurs naturally,” says Albert Tsai, M.D/ Ph.D. candidate at the Keck School of Medicine and the lead author of the study.

Expanding on previous work done at the Keck School and USC Norris Comprehensive Cancer Center and elsewhere, researchers studied patient tumor chromosomal translocations to gain an important clue as to how the most common lymphomas are caused. The study demonstrated that these breaks are focused at CpG sites, short special sequences in the genome, within restricted breakage zones. The CpG localization occurs in early B-cells, but not in translocations before or after that stage.

Their findings implicated roles for two enzymes - AID and RAG complex - which are normally present in lymphocytes and that function to diversify the immune system to defend against attack by bacteria, viruses and parasites, Lieber says. The diversification process involves altering the DNA which encodes antibodies, by cutting and rejoining the DNA in a way that sometimes goes awry. This appears to be what causes the chromosomal translocations, he says.

“Based on previous clues, we did a number of biochemical studies to verify our hunch about the mechanism of translocation,” Lieber says. “Our study demonstrates the biochemical feasibility of the sequence of events proposed, and this matches the fingerprint left by the chromosomal translocations.”

http://www.usc.edu/

Link




The human immune system is in a perpetual state of self-experimentation. It expertly mutates and shuffles the DNA of its own cells to evolve new defenses against the vast array of microbes that try to invade our bodies. But when the genetic experiment goes awry, the result can be a deadly cancer. Now, Rockefeller

Full Post: An enzyme that mutates antibodies also targets a cancer-causing oncogene



A newly published genome sequence of a breast cancer cell line reveals a heavily rearranged genetic blueprint involving breaks and fusions of genes and a broken DNA repair machinery, said researchers at Baylor College of Medicine in a report that appears online in the journal Genome Research. “It’s like a computer program that has become

Full Post: Breast cancer genome shows instability of cancer



Researchers at the University of Southern California (USC) have found that inactivating a specific biomarker for aggressive prostate cancer blocks the development of prostate cancer in animal models. Researchers say the upcoming study in the Proceedings of the National Academy of Sciences - now available online - may lead to a novel cancer therapy

Full Post: Discovery of novel approach to suppress prostate cancer progression



Roche NimbleGen, Inc. has launched NimbleGen Comparative Genomic Hybridization (CGH) microarrays in a 12×135K format for analysis of DNA copy number variation. NimbleGen CGH 12×135K arrays allow simultaneous analysis of 12 independent sample pairs on a single microarray slide, each with 135,000 empirically tested long oligonucleotide probes. This new array format will enable rapid and

Full Post: Roche NimbleGen launches microarrays for analysis of DNA copy number variation



The novel design of a deep muscle along the spinal column called the multifidus muscle may in fact be key to spinal support and a healthy back, according to researchers at the University of California, San Diego School of Medicine. Their findings about the potentially important “scaffolding” role of this poorly understood muscle has been

Full Post: Multifidus muscle design contributes to spine stability