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National Institute of Environmental Health Sciences (NIEHS)

Media Availability — August 10 – 24, 2015

FOR IMMEDIATE RELEASE
Monday, August 10, 2015, 11:00 a.m. EDT
Contact: Robin Arnette, NIEHS
(919) 541 - 5143

NIEHS Scientists Identify the Immunity Proteins That Cause a Majority of DNA Damage in Several Types of Human Cancers

New research published online August 10 in the journal Nature Genetics found that a mutation-causing enzyme known as APOBEC3A (A3A) may be the main cause of mutations in certain cancers. Previous work from other groups implicated another APOBEC enzyme, known as APOBEC3B (A3B).

Corresponding author Dmitry Gordenin, Ph.D., head of the NIEHS Mechanisms of Genome Dynamics Group, will be available for interviews on this new finding Monday, August 10 through Monday, August 24.

Study Background:

APOBEC proteins perform an important function in the immune system, by restricting the spread of viruses within the body. However, a subset of these proteins produces the majority of DNA mutations in certain cancers, according to a team led by researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. The scientists previously found that APOBEC enzymes were responsible for a substantial number of mutations in 80-90 percent of bladder and cervical cancers, and 20-30 percent of head and neck, breast, and lung cancers.

In this new study, NIEHS scientists went further by engineering two varieties of yeast. One strain produced APOBEC3A (A3A) and the other produced A3B. Once team members identified the DNA sequences that each APOBEC preferentially mutated in yeast, they used the findings to mine data from The Cancer Genome Atlas, a cancer database funded and managed by the National Cancer Institute and the National Human Genome Research Institute.

The study concluded that in cancer samples with a high number of APOBEC-induced mutations, A3A caused 10 times as many DNA sequence changes than A3B. In samples with small numbers of APOBEC mutations, A3B was responsible. The results could have far-reaching implications for diagnosis and personalized treatment of cancers.

These discoveries were made, in part, using an analytical package developed by the NIEHS Integrative Bioinformatics Support Group led by David Fargo, Ph.D.

Additional Information:

This video, produced by Research Square in collaboration with Nature Publishing Group, depicts the findings of this research. http://youtu.be/PgTxhUKqwmc


Grant Number:
Z1AES103266
U24CA143845
R01GM052319
1P01CA120964
R00ES022633
K99ES024424


Reference: Chan K, Roberts SA, Klimczak LJ, Sterling JF, Saini N, Malc EP, Kim J, Kwiatkowski DJ, Fargo DC, Mieczkowski PA, Getz G, Gordenin DA. 2015. An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers. Nat Genet; doi: 10.1038/ng.3378 [Online 10 August 2015]. [Abstract]


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