Cancer: BRCA2 and resistance to therapy

Summaries of newsworthy papers include Undetectable ocean trends, Physics at the beach, DNA proves its potential, Genome-wide view of prostate cancer risk, fMRI tracks monkey ‘voice’ area, How HIV ravages gut immune cells


For papers that will be published online on 10 February 2008

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Cancer: BRCA2 and resistance to therapy – Nature

Undetectable ocean trends – Nature Geoscience

Physics at the beach – Nature Materials
DNA proves its potential – Nature Nanotechnology

Genome-wide view of prostate cancer risk – Nature Genetics

fMRI tracks monkey ‘voice’ area – Nature Neuroscience

How HIV ravages gut immune cells – Nature Immunology

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of Press contacts for the Nature journals are listed at the end of this release.

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[1] & [2] Cancer: BRCA2 and resistance to therapy

DOI: 10.1038/nature06548

DOI: 10.1038/nature06633

Scientists have gained new insight into how changes in BRCA2 can affect a cancer’s resistance to therapy. BRCA2 mutations are associated with an increase in breast and ovarian cancer risk, as the gene’s normal function is to repair damaged DNA. But these cancer-causing faults are bad news for the tumour itself, as they also render it sensitive to DNA-damaging chemotherapy drugs like cisplatin. Unfortunately, many BRCA2 tumours develop resistance to cisplatin.

Two papers published online in Nature this week reveal how this resistance occurs. The teams, led by Alan Ashworth and Toshiyasu Taniguchi, show that some cancer cells can acquire secondary ‘reactivating’ mutations in their BRCA2 gene, switching it back on and allowing the cancer to repair the DNA damaged by the drug’s assault. Such mutations were found in several cisplatin-resistant ovarian cancer patients. The discovery raises the possibility that blocking BRCA2 function in such patients might allow doctors to overcome drug resistance and continue with cisplatin treatment.

Author contact:

Alan Ashworth (The Institute of Cancer Research, London, UK)
Tel: +44 20 7153 5333; E-mail: [email protected] Author paper [1]

Toshiyasu Taniguchi (Fred Hutchinson Cancer Research Center, Seattle, WA, USA)

Tel: +1 206 667 7283; E-mail: [email protected] Author paper [2]

****************************************NATURE GEOSCIENCE******************************************


[3] Undetectable ocean trends

DOI: 10.1038/ngeo126

True changes in the North Atlantic Ocean circulation due to climate change are nearly impossible to identify, according to research published online this week in Nature Geoscience. This is due to the background variability caused by naturally occurring eddies. The findings imply that measurements in three dimensions over several decades would be necessary to determine whether climate change has affected the ocean’s circulation.

Carl Wunsch has estimated the variability in transport volume that is theoretically expected from eddies that are known to occur in the ocean. He finds that random fluctuations of about 20 million cubic metres per second of water can arise from such eddy activity on an ocean-wide scale and can persist over several years. Such fluctuations could easily be mistaken for a global warming-induced trend.

Author contact:

Carl Wunsch (Massachusetts Institute of Technology, Cambridge, MA, USA)

Tel: +1 617 253 5937; E-mail: [email protected]

Other papers from Nature Geoscience to be published online at the same time and with the same embargo:

[4] Columbia River flood basalts from a centralized crustal magmatic system

DOI: 10.1038/ngeo124

********************************************* NATURE MATERIALS ************************************** (

[5] Physics at the beach

DOI: 10.1038/nmat2117

Scientists have proposed an explanation for why structures such as sandcastles can be built so easily without a recipe for the exact combination of sand and water needed. The study, online this week in Nature Materials, should prove useful for clarifying how grain–liquid–air interfaces interact.

The insensitivity of the mechanical properties of wet granular matter to their liquid content is not well understood. Stephan Herminghaus and colleagues used X-ray microtomography to demonstrate that this behaviour results from the organization of the liquid in the grain pile into a variety of bridges and clusters. For spherical as well as non-spherical grains, such as sand, a simple geometric rule relating the macroscopic properties, for example stability, to the internal liquid morphologies is proposed.

Such imaging techniques could clarify how grain–liquid–air interfaces interact and possibly prevent grain segregation, particle agglomeration and even landslides.

Author contact:

Stephan Herminghaus (Max Planck Institute, Göttingen, Germany)

Tel: +49 551 517 6200; E-mail: [email protected]

Other papers from Nature Materials to be published online at the same time and with the same embargo:

[6] Orientation-dependent ionization energies and interface dipoles in ordered molecular assemblies

DOI: 10.1038/nmat2119

**************************************NATURE NANOTECHNOLOGY***********************************


[7] DNA proves its potential


The electrical conductivity of an individual DNA molecule can be measured by wiring it into a nanoscale circuit, reports a study published online this week in Nature Nanotechnology. This work suggests that the electronic properties of a fully base-paired double helix are comparable to those of a similarly sized stack of graphite.

A team led by Colin Nuckolls and Jacqueline Barton made a tiny electronic device in which part of the circuit is formed by a single-walled carbon nanotube. Cutting a very small gap in the nanotube opened the circuit and current stopped flowing through the device. When this gap was bridged with a DNA molecule, however, the conductive path was restored and the electrical properties of the DNA could be measured. It was shown that even a single base-pair mismatch in a double helix led to a significant decrease in conductivity.

The flow of current could be stopped by cutting the bridging DNA with an enzyme. This suggests that the DNA adopts its usual shape, rather than being distorted by the device, and therefore that the conductivity is not simply an artifact of the measuring technique.

Author contacts:
Colin Nuckolls (Columbia University, New York, NY, USA)
Tel: +1 212 854 6289; E-mail: [email protected]

Jacqueline Barton (California Institute of Technology, Pasadena, CA, USA) Co-author
Tel: +1 626 395 6075; E-mail: [email protected]

Other papers from Nature Nanotechnology to be published online at the same time and with the same embargo:

[8] High-resolution detection of Au catalyst atoms in Si nanowires


***********************************************NATURE GENETICS **************************************


[9], [10] & [11] Genome-wide view of prostate cancer risk

DOI: 10.1038/ng.90

DOI: 10.1038/ng.91

DOI: 10.1038/ng.89

At least ten newly identified genetic variants are associated with increased susceptibility to prostate cancer, according to three studies to be published online this week in Nature Genetics. These findings double the number of variants known to be associated with risk of prostate cancer, and, in the future, may allow predictions of high risk in particular individuals.

The three groups independently carried out genome-wide association studies of thousands of individuals with or without prostate cancer. Rosalind Eeles and colleagues identified seven loci that were significantly associated with the disease on chromosomes 3, 6, 7, 10, 11, 19 and X. Stephen Chanock and colleagues report risk loci on chromosomes 7, 10 (two loci) and 11, as well as nine other loci showing suggestive association. Julius Gudmundsson’s team reports risk loci on chromosomes 2 and X. Each group’s findings were replicated in an independent population, and each confirmed previous susceptibility loci on chromosomes 8 and 17.

Although the specific genes that are affected by these variants have not yet been pinpointed, the authors of the studies note a few candidates. One of the risk variants on chromosome 10 is just upstream of MSMB, which encodes a protein that is produced in the prostate, and loss of MSMB expression is associated with recurrence of disease after prostatectomy. The variant on chromosome 19 is near KLK3, which encodes PSA, an enzyme that liquefies semen and is used as a standard serum marker for screening and disease monitoring.

Author contacts:

Rosalind Eeles (The Institute of Cancer Research, Sutton, UK) Author paper [9]

Tel: +44 181 642 6011; E-mail: [email protected]

Stephen Chanock (National Institutes of Health, Bethesda, MD, USA) Author paper [10]

Tel: +1 301 435 7559; E-mail: [email protected]

Julius Gudmundsson (deCODE Genetics, Reykjavik, Iceland) Author paper [11]

Tel: +354 570 1900; E-mail: [email protected]

Edward Farmer (deCODE Genetics, Reykjavik, Iceland) Media contact paper [11]

Tel: +1 212 343 2819; E-mail: [email protected]

Berglind Olafsdottir (deCODE Genetics, Reykjavik, Iceland) Media contact paper [11]

Tel: +354 570 2393; E-mail: [email protected]

Other papers from Nature Genetics to be published online at the same time and with the same embargo:

[12] MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis

DOI: 10.1038/ng.82

[13] Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome)

DOI: 10.1038/ng.2007.66

*******************************************NATURE NEUROSCIENCE ***********************************


[14] fMRI tracks monkey ‘voice’ area

DOI: 10.1038/nn2043

fMRI scanning, rarely used in non human primates, has been used to support the idea of a ‘voice’ area in rhesus monkeys. The technique tracks changes in blood flow as a measure of neural activity, and although it is common in human studies, the need to keep subjects still during the experiment makes it challenging to use on awake animals.

In the study published this week in Nature Neuroscience, Christopher Petkov and colleagues were able to track neural activity in two monkeys as they heard sounds produced by their own species, sounds produced by other animals (including other primate species), natural sounds (such as thunder), and scrambled versions of all of these sounds. A region in the anterior superior temporal cortex was found to be activated more strongly in response to sounds from the monkeys’ own species than to the other sounds. This finding suggests that monkeys, like humans, may have brain areas specialized for processing species-specific vocalizations.

Imaging study in humans have identified a voice-sensitive area in the brain, but previous attempts to find a similar area in monkeys have produced conflicting results, which had led to the suggestion that such a voice-sensitive area might be specific to humans.

Author contact:

Christopher Petkov (Max-Planck Institute for Biological Cybernetics, Tuebingen, Germany)
Tel: +49 7071 601 659; E-mail: [email protected]

Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:

[15] Control of visually guided behaviour by distinct populations of spinal projection neurons
DOI: 10.1038/nn2048

*******************************************NATURE IMMUNOLOGY ************************************


[16] How HIV ravages gut immune cells

DOI: 10.1038/ni1566

The specific interaction between HIV and gut-associated immune cells, which may promote the depletion of cells and the virus’ devastating attack on the immune system, is reported a study online in Nature Immunology.

James Arthos and colleagues find that HIV interacts specifically with gut-associated immune cells in a way that promotes cell-to-cell spread of HIV infection. This occurs by specific interaction between HIV gp120 protein and a gut-associated protein that promotes lymphocyte migration to the gut. Interaction between these two proteins alters immune lymphocytes, making them much more susceptible to infection and, thus death and depletion.

This key finding may help explain why HIV infection leads to such massive depletion of gut-associated immune cells. It may also lead to new avenues of research to find ways to prevent this type of HIV-mediated immune destruction.

Author contact:

James Arthos (National Institutes of Health Laboratory of Immunoregulation, Bethesda, MD,


Tel: +1 301 496 4553; E-mail: [email protected]

Other papers from Nature Immunology to be published online at the same time and with the same embargo:

[17] The proteolytic activity of the paracaspase MALT1 is key in T cell activation

DOI: 10.1038/ni1568


Items from other Nature journals to be published online at the same time and with the same embargo:


[18] Adenosyltransferase tailors and delivers coenzyme B12

DOI: 10.1038/nchembio.67

Nature PHYSICS (

[19] Optically mapping the electronic structure of coupled quantum dots

DOI: 10.1038/nphys882

[20] Coarsening of granular segregation patterns in quasi-two-dimensional tumblers

DOI: 10.1038/nphys881


[21] Interleukin-22 mediates mucosal host defense against Gram-negative bacterial pneumonia

DOI: 10.1038/nm1710

[22] Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens

DOI: 10.1038/nm1720

[23] Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain

DOI: 10.1038/nm1723


[24] OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1–SEL1L ubiquitin ligase complex for ERAD

DOI: 10.1038/ncb1689

[25] Enucleation of cultured mouse fetal erythroblasts requires Rac GTPases and mDia2

DOI: 10.1038/ncb1693

[26] Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin

DOI: 10.1038/ncb1695

[27] A core Klf circuitry regulates self-renewal of embryonic stem cells

DOI: 10.1038/ncb1698


[28] Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins

DOI: 10.1038/nsmb.1382

[29] The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules

DOI: 10.1038/nsmb.1384

[30] HP1-mediated transcriptional silencing targets the major Pol II coactivator complexes

DOI: 10.1038/nsmb.1385

[31] Identification of conjugation specificity determinants unmasks vestigial preference for ubiquitin within the NEDD8 E2

DOI: 10.1038/nsmb.1387


[32] Tractable Cre-lox system for stochastic alteration of genes in mice

DOI: 10.1038/nmeth1183

[33] Generating somatic mosaicism with a Cre recombinase-microsatellite sequence transgene

DOI: 10.1038/nmeth1182

[34] Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex

DOI: 10.1038/nmeth1184



The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

Canberra: 5

Carlton: 9

Parkville: 9


Nanjing: 27


Helsinki: 10


Grenoble: 5

Kremlin Bicetre: 13

Montfermeil: 13

Paris: 10, 13


Berlin: 6

Erlangen: 5

Goettingen: 5

Hamburg: 6

Tubingen: 14


Reykjavik: 11


Genoa: 16


Hiroshima: 33

Nagoya: 26

Tokyo: 21


Arnhem: 11

Nijmegen: 11


Singapore: 25, 27


Zaragoza: 11


Stockholm: 11

Umea: 11


Epalinges: 17

Geneva: 17

Lausanne: 17


Ankara: 33


Birmingham: 8

Bristol: 9

Cambridge: 9

Daresbury: 8

London: 1, 9

Manchester: 14

Nottingham: 9

Sheffield: 9

Sutton: 9



Los Angeles: 2, 29, 30, 32

Menlo Park: 24

Pasadena: 7

San Francisco: 22

Stanford: 24


Aurora: 34

Boulder: 34

Denver: 10

Fort Collins: 28

District of Columbia

Washington: 19


Atlanta: 10, 29

Savannah: 1


Chicago: 11

Evanston: 8, 20

Urbana: 27


West Lafayette: 28


New Orleans: 21


Baltimore: 11

Bethesda: 10, 16

Frederick: 10, 16

Gaithersburg: 10


Boston: 10, 11, 15, 23

Cambridge: 3, 15, 20, 25

Charlestown: 23

Ipswich: 30


Ann Arbor: 18, 33


Rochester: 2, 11


Chesterfield: 22

Kansas City: 12

St Louis: 10, 11, 28


Lincoln: 18

New York

New York: 1, 7, 26, 30

North Carolina

Winston-Salem: 11


Eugene: 12

Portland: 32


Pittsburgh: 21


Memphis: 31

Nashville: 11


Ellensburg: 4

Pullman: 4

Seattle: 2, 16


For media inquiries relating to embargo policy for all the Nature Research Journals:

Katherine Anderson (Nature London)

Tel: +44 20 7843 4502; E-mail: [email protected]

Ruth Francis (Senior Press Officer, Nature, London)

Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Cell Biology (London)

Bernd Pulverer

Tel: +44 20 7843 4892; E-mail: [email protected]

Nature Chemical Biology (Boston)

Andrea Garvey

Tel: +1 617 475 9241, E-mail: [email protected]

Nature Genetics (New York)

Orli Bahcall

Tel: +1 212 726 9311; E-mail: [email protected]

Nature Geoscience (London)

Heike Langenberg

Tel: +44 20 7843 4042; E-mail: [email protected]

Nature Immunology (New York)

Laurie Dempsey

Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)

Alison Stoddart

Tel: +44 20 7843 4593; E-mail: [email protected]

Nature Medicine (New York)

Juan Carlos Lopez

Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)

Allison Doerr

Tel: +1 212 726 9393; E-mail: [email protected]

Nature Nanotechnology (London)

Peter Rodgers

Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)

Sandra Aamodt (based in California)

Tel: +1 530 795 3256; E-mail: [email protected]

Nature Physics (London)

Alison Wright

Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)

Michelle Montoya

Tel: +1 212 726 9326; E-mail: [email protected]

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Published: 10 Feb 2008

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