Common Molecular 'Signature' Identified In Solid = Tumors

From: Subject: Common Molecular 'Signature' Identified In Solid Tumors Date: Sun, 21 May 2006 11:31:24 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_006A_01C67CCA.17307ED0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_006A_01C67CCA.17307ED0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://researchnews.osu.edu/archive/soldtumr.htm Common Molecular 'Signature' Identified In Solid = Tumors

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OSU News = Research=20 Archive Search an archive of past research = stories.=20
Coverage of OSU = Research=20
Reports on national = news coverage=20 of university research.=20
Research Communications=20 Staff Who = we are and=20 what we do.=20



(Last updated 1/25/06) =

Previous stories = pertaining to=20 Professor Croce's research:

"Role Of = microRNA=20 Identified In Thyroid Cancer," 12/24/05.

"Activity Of = Unusual Genes Distinguishes Dangerous Leukemia," = 10/28/05.=20

"Unusual RNAs = Linked To Chronic Leukemia, May Help Treat It," 9/12/05. =

"Role = of=20 MicroRNA Identified In Breast Cancer," 8/10/05.

"Building A=20 Better Mouse Model Of Lung Cancer: FHIT Counts," 7/29/05.=20

"New = Tumor=20 Suppressor Gene Linked To Cancer Predisposition," 4/12/05.=20

[Embargoed until 5:00 P.M. ET, Monday, January 30, to = coincide=20 with online publication in the Proceedings of the National = Academy of=20 Sciences.]

COMMON MOLECULAR =91SIGNATURE' IDENTIFIED IN SOLID TUMORS

COLUMBUS, Ohio =96 Scientists have discovered that a wide = variety of=20 different cancers actually share something in common =96 a = molecular=20 =93signature=94 made up of tiny bits of genetic material called = microRNA=20 (miRNA) that target key cancer genes and promote malignant growth. =

The finding provides more insight into miRNA as an emerging = class of=20 gene regulators and may also pave the way for new approaches in = diagnosis=20 and treatment.

Carlo Croce =

The study appears online in the Proceedings of the National = Academy of=20 Sciences.

Scientists have only recently begun to understand how important = microRNA may be in regulating gene expression. For years, these = tiny bits=20 of genetic material went unnoticed =96 nestled within vast = stretches of the=20 genome that appeared to be non-functional. They may have been easy = to=20 overlook: miRNAs are usually only 22 or so nucleotides in length = =96=20 miniscule in size when compared to their cousins, messenger RNA, = which can=20 be several hundred to a thousand times that long.

But several years ago, researchers studying roundworms noted = that=20 properly functioning miRNA was necessary for normal development. = Since=20 then, scientists in laboratories around the world have identified = hundreds=20 of miRNAs and found that they are highly conserved over time =96 = meaning=20 that they show up in generation after generation in everything = from plants=20 to mice to humans =96 confirming their important roles in growth = and=20 survival.

Carlo=20 Croce, professor and chair of molecular virology, = immunology and=20 medical genetics at The Ohio State University and the first = researcher=20 to discover miRNA involvement in human cancer, had a hunch that = there=20 might be shared patterns of miRNA among certain cancers. Under his = direction, researchers looked for miRNA activity, or expression, = in 540=20 samples of lung, breast, stomach, prostate, colon and pancreatic = tumors=20 and in the normal tissue surrounding them.

Croce says = finding such a=20 signature is important because it shows that many forms of = cancer=20 share common genetic pathways that become scrambled as = cancer takes=20 hold and spreads. He says narrowing the list of the most = active ones=20 provides a guide to directing future research. =

Using microarray technology developed at Ohio State , lead=20 investigators Stefano Volinia and George Calin found 137 different = miRNAs=20 expressed in at least half of the cancers, with 43 miRNAs allowing = scientists to distinguish the difference between normal and = malignant=20 tissue.

Further tests showed that 21 of the distinguishing miRNAs were=20 deregulated in at least three of the cancers =96 and in some = cases, as many=20 as five or all six. The researchers defined this limited set as = the =93miRNA=20 signature=94 in solid tumors.

Croce says finding such a signature is important because it = shows that=20 many forms of cancer share common genetic pathways that become = scrambled=20 as cancer takes hold and spreads. He says narrowing the list of = the most=20 active ones provides a guide to directing future research.

=93We know that there are hundreds of miRNAs, and some of them = may have=20 multiple gene targets. Finding the ones that appear over and over = again in=20 various forms of cancer will help us design new and better = interventions,=94=20 says Croce.

MiRNAs can behave like oncogenes, which promote tumor growth, = or tumor=20 suppressors, which keep potentially malignant cells in check. = Croce points=20 out that miRNA activity is tissue-sensitive, meaning some miRNAs = may be=20 overexpressed, or =93turned on=94 in some of the cancers while in = others they=20 are underexpressed, or =93turned off.=94

In the six types of cancer in the study, the majority (26) of = the=20 miRNAs were overexpressed, while 17 were underexpressed.

Calin and Volinia also identified several key cancer genes the = miRNA=20 signature targets, including the tumor suppressors = retinoblastoma-1 (RB1)=20 and transforming growth factor, beta receptor 2 (TGFBR2).

Croce predicts that miRNAs themselves may one day be used as=20 treatments. =93If we can replace miRNAs that are lost and block = those that=20 are overly abundant, then maybe we can prevent some of the very = earliest=20 changes that happen in the development of cancer. There is a lot = of work=20 that still needs to be done, but I am convinced that this field = will give=20 us more precise and less toxic ways of dealing with cancer than we = have=20 today =96 even considering some of our new, molecularly-targeted = therapies.=94=20 Support from the research came from the National Cancer Institute, the = Italian=20 Ministry of Public Health, the Italian Ministry of University = Research=20 Telethon, the Italian Association for Cancer Research and a Kimmel = Scholar=20 award to George Calin.

Contact: Michelle Gailiun, Medical Center Communications, = 614-293-3737,=20 or Gailiun.1@osu.edu

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