From: Sukie Crandall
Date: 2011-01-22 22:31:34 UTC
Subject: [ferrethealth] islet cell tumors (There is also work on some of these genetics ongoing in ferrets.)
To: fhl <firstname.lastname@example.org>
breakthrough: islet cell tumor genetics in humans
Put in because this is a situation where physiologically and genetically th=
ere could be an overlap for ferrets, AND because ferrets DO vary a decent b=
it with insulinoma so there might be some hints about that in this, too.
> Public release date: 21-Jan-2011
> Johns Hopkins Medical Institutions
> Johns Hopkins scientists crack genetic code for form of pancreatic cancer
> Scientists at Johns Hopkins have deciphered the genetic code for a type o=
f pancreatic cancer, called neuroendocrine or islet cell tumors. The work, =
described online in the Jan. 20 issue of Science Express, shows that patien=
ts whose tumors have certain coding "mistakes" live twice as long as those =
> "One of the most significant things we learned is that each patient with =
this kind of rare cancer has a unique genetic code that predicts how aggres=
sive the disease is and how sensitive it is to specific treatments," says N=
ickolas Papadopoulos, Ph.D., associate professor at the Johns Hopkins Kimme=
l Cancer Center and director of translational genetics at Hopkins' Ludwig C=
enter. "What this tells us is that it may be more useful to classify cancer=
s by gene type rather than only by organ or cell type."
> Pancreatic neuroendocrine cancers account for about five percent of all p=
ancreatic cancers. Some of these tumors produce hormones that have noticeab=
le effects on the body, including variations in blood sugar levels, weight =
gain, and skin rashes while others have no such hormone "signal."
> In contrast, hormone-free tumors grow silently in the pancreas, and "many=
are difficult to distinguish from other pancreatic cancer types," accordin=
g to Ralph Hruban, M.D., professor of pathology and oncology, and director =
of the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins.
> For the new study, the team investigated non-hormonal pancreatic neuroend=
ocrine tumors in 68 men and women. Patients whose tumors had mutations in t=
hree genes =96 MEN-1, DAXX and ATRX =96 lived at least 10 years after diagn=
osis, while more than 60 percent of patients whose tumors lacked these muta=
tions died within five years of diagnosis.
> The Johns Hopkins team, which previously mapped six other cancer types, u=
sed automated tools to create a genetic "map" that provides clues to how tu=
mors develop, grow and spread.
> Within the code are individual chemicals called nucleotides, which pair t=
ogether in a pre-programmed fashion to build DNA and, in turn, a genome. Co=
mbinations of these nucleotide letters form genes, which provide instructio=
ns that guide cell activity. Changes in the nucleotide pairs, called mutati=
ons, can create coding errors that transform a normal cell into a cancerous=
> In the first set of experiments, the Johns Hopkins scientists sequenced n=
early all protein-encoding genes in 10 of the 68 samples of pancreatic neur=
oendocrine tumors and compared these sequences with normal DNA from each pa=
tient to identify tumor-specific changes or mutations.
> In another set of experiments, the investigators searched through the rem=
aining 58 pancreatic neuroendocrine tumors to determine how often these mut=
ated genes appeared.
> The most prevalent mutation, in the MEN-1 gene, occurred in more than 44 =
percent of all 68 tumors. MEN-1, which has been previously linked to many c=
ancers, creates proteins that regulate how long strands of DNA are twisted =
and shaped into dense packets that open and close depending on when genes n=
eed to be activated. Such a process is regulated by proteins and chemicals =
that operate outside of genes, termed "epigenetic" by scientists.
> Two other commonly mutated genes, DAXX and ATRX, which had not previously=
been linked to cancer, also have epigenetic effects on how DNA is read. Of=
the samples studied, mutations in DAXX and ATRX were found in 25 percent a=
nd 17.6 percent, respectively. The proteins made by these two genes interac=
t with specific portions of DNA to alter how its chemical letters are read.
> "To effectively detect and kill cancers, it may be important to develop n=
ew diagnostics and therapeutics that take aim at both epigenetic and geneti=
c processes," says Kenneth Kinzler, Ph.D., professor of oncology at the Joh=
ns Hopkins Kimmel Cancer Center and co-director of the Ludwig Center at Joh=
> The Johns Hopkins team also found that 14 percent of the samples studied =
contained mutations in a gene family called mTOR, which regulates cell sign=
aling processes. Papadopoulos says that patients with tumors containing suc=
h alterations in the mTOR pathway could be candidates for treatment with mT=
OR inhibitor drugs.
> "This is a great example of the potential for personalized cancer therapy=
," says Hruban. "Patients who are most likely to benefit from a drug can be=
identified and treated, while patients whose tumors lack changes in the mT=
OR pathway could be spared the side effects of drugs that may not be effect=
ive in their tumors."
> Papadopoulos, Kinzler, and co-authors Bert Vogelstein, Luis Diaz, and Vic=
tor Velculescu are co-founders and members of the scientific advisory board=
of Inostics, a company that is developing technologies for the molecular d=
iagnosis of cancer. They own Inostics stock, which is subject to certain re=
strictions under the Johns Hopkins University's conflict of interest policy=
. Kinzler, Vogelstein and Velculescu are entitled to shares of any royaltie=
s received by the University on sales of products related to genes describe=
d in this manuscript.
> Major funding for the study was provided by the Caring for Carcinoid Foun=
dation, a nonprofit foundation which funds research on carcinoid cancer, pa=
ncreatic neuroendocrine cancer, and related neuroendocrine cancers. Additio=
nal funding was from the Lustgarten Foundation for Pancreatic Cancer Resear=
ch, the Sol Goldman Pancreatic Cancer Research Center, the Joseph Rabinowit=
z Fund for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund fo=
r Cancer Research, the Raymond and Beverly Sackler Research Foundation, the=
AACR Stand Up to Cancer's Dream Team Translational Cancer Research Grant a=
nd the National Institutes of Health.
> Co-authors include Yuchen Jiao, Chanjuan Shi, Barish Edil, Roeland de Wil=
de, David Klimstra, Anirban Maitra, Richard Schulick, Laura Tang, Christoph=
er Wolfgang, Michael Choti, Victor Velculescu, Luis Diaz Jr., and Bert Voge=
lstein from Johns Hopkins.
> On the Web:
> The Sol Goldman Pancreatic Cancer Research Center: http://pathology.jhu.e=
> Science: http://www.sciencemag.org/
> Caring for Carcinoid Foundation: www.caringforcarcinoid.org
Sukie (not a vet)
Recommended ferret health links:
all ferret topics:
"All hail the procrastinators for they shall rule the world tomorrow."
(2010, Steve Crandall)
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