From:
Sukie Crandall
Date: 2008-03-03 18:48:27 UTC
Subject: [ferrethealth] Re: Chordoma
To: ferrethealth@yahoogroups.com
I am going to look it up, too, but this question intrigued me so I
have asked some others if some lines are more genetically vulnerable
to developing chordomas, or if this may simply a coincidence, and I
pointed them to your post.
Part of what i have to wonder is if incomplete neural coverage might
make a chordoma more likely to occur. (NOTHING MORE THAN A WILD GUESS
-- SEE LATER IN POST THAT IT WAS WRONG.) If so, then genetic lines
might matter but so does nutrition. Among humans too low amounts of
folic acid during pregnancy can lead to increased rates of spina
bifida, for example.
I'll pass http://www.afip.org/ferrets/chordoma.html
has some info on chordomas and you already know that there is info in
the FHL Archives.
This is a VERY interesting question.
Okay, I pulled up Pub Med for abstracts and YES, there CAN be genetic
vulnerabilities, with some idea now what the mutation is.
(I think my wild guess was very wrong...)
Is the c-KIT the same KIT neural crest genetic variation that is
considered to be a highly possible candidate for the markings of a
number of fancies like pandas, blazes, and those with extraneous
bodily white patches?
BEGIN QUOTES
Cancer Biol Ther. 2005 Nov;4(11):1270-4. Epub 2005 Nov 18.
Comment in:Cancer Biol Ther. 2005 Dec;4(12):1417-8.Activating
mutations in c-KIT and PDGFRalpha are exclusively found in
gastrointestinal stromal tumors and not in other tumors overexpressing
these imatinib mesylate target genes.
Burger H, den Bakker MA, Kros JM, van Tol H, de Bruin AM,Oosterhuis W,
van den Ingh HF, van der Harst E, de Schipper HP, Wiemer EA, Nooter K.
Department of Medical Oncology, Erasmus Medical Center Rotterdam-
Josephine Nefkens Institute, Rotterdam, The Netherlands.
Previous studies have shown that Imatinib mesylate (Gleevec), a
selective tyrosine kinase inhibitor of c-KIT and platelet-derived
growth factor receptors (PDGFR), is highly effective in c-KIT/CD117-
positive gastrointestinal stromal tumors (GIST), especially in those
having activating mutations in c-kit exon 11. In addition, gain-of-
function mutations in the juxtamembrane domain (exon 12) and the
kinase activation loop (exon 18) of PDGFRalpha were found in GISTs.
Importantly, the presence and type of these mutually exclusive c-KIT
or PDGFRalpha mutations were found to be associated with the response
to imatinib. Here, we examined the prevalence of c-kit exon 11 and
PDGFRalpha exons 12 and 18 mutations in other tumor types known to
express these tyrosine kinase receptors in order to explore which
other cancer types may potentially benefit from imatinib treatment. We
determined the mutational status of these commonly mutated exons by
direct sequencing in 11 different tumor types (in total: 215 unrelated
cases), including GIST, chordoma, and various distinct tumors of lung,
brain and its coverings, and skin cancer. Of the 579 exons examined
(211 c-kit exon 11, 192 PDGFRalpha exon 12, 142 PDGFRalpha exon18, 17
PDGFRbeta exon 12 and 17 PDGFRbeta exon 18), only 12 (all GIST)
harbored mutations (10 c-kit exon 11 and 2 PDGFRalpha exon18). From
these data we conclude that activating c-KIT and PDGFR mutations are
sporadic in human cancers known to overexpress these tyrosine kinase
receptor genes and suggest that, except in GIST, this overexpression
is not correlated with activating mutations. The latter may imply that
these wild-type c-KIT and PDGFR tumor types will probably not benefit
from imatinib treatment.
PMID: 16294026 [PubMed - indexed for MEDLINE]
Surg Neurol. 2007 Oct;68(4):425-30; discussion 430. Epub 2007 Aug 21.
New candidate chromosomal regions for chordoma development.
Bayrakli F, Guney I, Kilic T, Ozek M, Pamir MN.
Department of Neurosurgery and Institute of Neurological Sciences,
Istanbul 81326, Turkey.
BACKGROUND: Chordomas are rare, slow growing, infiltrative tumors
thought to arise from vestigial or ectopic notochord. Chordoma can
occur along the axial skeleton, predominantly in the sphenooccipital,
vertebral, and sacrococcygeal regions. Although most chordomas are
sporadic, familial cases have also been reported. The most common
molecular cytogenetic abnormalities in these tumors are monosomy of
chromosome 1 and gain of chromosome 7. In addition, a variety of other
chromosomal changes, which are associated with losses and gains of
different chromosomes, have also been described in chordomas, such as
1q, 2p, 3p, 5q, 9p, 10, 12q, 13q, 17, and 20q. METHODS: In this study,
using molecular cytogenetics (iFISH), we have studied 1p36, 1q25, 3p13-
p14, 7q33, 17p13.1 (p53 gene locus), 2p13 (TGF-alpha locus), 6p12
(VEGF locus), and 4q26-q27 (bFGF/FGF2 locus) loci in chordoma tissues
from seven patients with 7 primary tumors and 11 recurrences. RESULTS:
We found that chromosomes 1p36, 1q25, 2p13, and 7q33 are affected in
primary chordomas, and these aberrations persist in recurrences.
However, the chromosome 6p12 aberration was seen only in primary
chordomas, but not in recurrences, indicating that this locus may be
associated with chordoma genesis. CONCLUSIONS: Our descriptive data
from interphase FISH analyses suggest that future studies should
incorporate a larger number of patients and should focus on
identifying the candidate genes in chordoma pathogenesis. Such studies
may use a whole-genomic approach, in addition to the regions
identified in this study and others.
PMID: 17714767 [PubMed - indexed for MEDLINE]
Spine. 2007 Aug 15;32(18):1969-73.
Overexpressions of nerve growth factor and its tropomyosin-related
kinase A receptor on chordoma cells.
Park JB, Lee CK, Koh JS, Lee JK, Park EY, Riew KD.
Department of Orthopaedic Surgery, Catholic University of Korea School
of Medicine, Seoul, Korea.
STUDY DESIGN: Immunohistochemistry and in situ apoptosis detection
assay were performed on chordoma and notochordal cells. OBJECTIVES: To
investigate the expression levels of nerve growth factor (NGF) and its
2 receptors, tropomyosin-related kinase A (TrkA) and p75, as well as
proliferation potential and apoptosis indexes in chordoma and
notochordal cells. SUMMARY OF BACKGROUND DATA: Chordomas arise from
primitive notochordal remnants. Why these notochordal remnants undergo
malignant transformation to chordoma remains unknown. The binding of
NGF to the TrkA receptor promotes cell survival, while its binding to
the p75 receptor triggers apoptosis. If there is simultaneous
expression of both receptors, the effect of TrkA supersedes and the
cells survive. METHODS: We examined 10 surgically obtained sacral
chordoma tissue samples to determine the expressions of NGF and TrkA
and p75 receptors as well as markers of cellular proliferation and
apoptosis. As controls, we used notochordal cells of L4-L5 discs
obtained from ten 1-month old rats. We quantified the expressions of
NGF and TrkA and p75 receptors as well as markers of cellular
proliferation and apoptosis for both groups, respectively. RESULTS:
Chordoma and notochordal cells both expressed NGF as well as TrkA and
p75 receptors. While the mean percentage of p75 receptor expression
was very similar between chordoma and notochordal cells (P = 0.394),
the mean percentages of TrkA and NGF expressions were significantly
higher in chordoma cells than in notochordal cells (both P = 0.002).
The mean proliferation potential index of chordoma cells was
significantly higher than in notochordal cells (P < 0.01). Conversely,
the mean apoptosis index of chordoma cells was significantly lower
compared with that of notochordal cells (P = 0.03). CONCLUSION: The
current results suggest that increased expressions of NGF and TrkA
receptor in chordoma cells might be a possible mechanism of malignant
transformation of notochordal remnants to chordoma by negating
apoptotic signal of p75 receptor.
PMID: 17700442 [PubMed - indexed for MEDLINE]
END QUOTES
Okay, there is NO indication that nutrition plays a role in chordoma.
MY GUESS WAS WRONG -- PLEASE, NOTE!
Our ISP keeps dropping out on us today so I can't also look up
chordoma and spina bifida
BUT since nothing came up with the nutrition search I strongly doubt
there is any connection between the two.
Sukie (not a vet)
Recommended ferret health links:
http://pets.groups.yahoo.com/group/ferrethealth/
http://ferrethealth.org/archive/
http://www.afip.org/ferrets/index.html
http://www.miamiferret.org/fhc/
http://www.ferretcongress.org/
http://www.trifl.org/index.shtml
http://homepage.mac.com/sukie/sukiesferretlinks.html
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