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Molecular Neuro-Oncology
Laboratory
David N. Louis, M.D.
Major Research Interest - Tumor
Molecular Genetics
The laboratory is involved in molecular
genetic study of astrocytomas and other forms of primary human brain
tumors, such as medulloblastomas, meningiomas, schwannomas, hemangiopericytomas
and pineal gland tumors.
Recent Publication:
"Histology-Based
Expression Profiling Yields Novel Prognostic Markers in Human Glioblastoma"
J Neuropathol Exp Neurol. 2005 Nov;64(11):948-955.
See PubMed
- Article
[pdf] Link
Dong S, Nutt CL,
Betensky RA, Stemmer-Rachamimov AO, Denko NC, Ligon KL, Rowitch
DH, Louis DN.
From Department
of Pathology, Cancer Center and Neurosurgical Service (SD, CLN,
AOS-R, DNL), Massachusetts General Hospital and Harvard Medical
School, Boston, Massachusetts; Department of Biostatistics (RAB),
Harvard School of Public Health, Boston, Massachusetts; Division
of Radiation and Cancer Biology (NCD), Department of Radiation Oncology,
Stanford, California; and Department of Pediatric Oncology (KLL,
DHR), Dana-Farber Cancer Institute, Boston, Massachusetts.
Although the prognosis
for patients with glioblastoma is poor, survival is variable, with
some patients surviving longer than others. For this reason, there
has been longstanding interest in the identification of prognostic
markers for glioblastoma. We hypothesized that specific histologic
features known to correlate with malignancy most likely express
molecules that are directly related to the aggressive behavior of
these tumors. We further hypothesized that such molecules could
be used as biomarkers to predict behavior in a manner that might
add prognostic power to sole histologic observation of the feature.
We reasoned that perinecrotic tumor cell palisading, which denotes
the most aggressive forms of malignant gliomas, would be a striking
histologic feature on which to test this hypothesis. We therefore
used laser capture microdissection and oligonucleotide arrays to
detect molecules differentially expressed in perinecrotic palisades.
A set of RNAs (including POFUT2, PTDSR, PLOD2, ATF5, and HK2) that
were differentially expressed in 3 initially studied, microdissected
glioblastomas also provided prognostic information in an independent
set of 28 glioblastomas that did not all have perinecrotic palisades.
On validation in a second, larger independent series, this approach
could be applied to other human glioma types to derive tissue biomarkers
that could offer ancillary prognostic and predictive information
alongside standard histopathologic examination.
Article supplemental
materials:
Links
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Neurosurgery
Clinical Units
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