Sign
out: Neuropathology surgicals and autopsies.
Research Interests:
Our laboratory investigates
the molecular genetic basis of human brain tumors.
Brain tumors are the second most frequent
malignancy of childhood and are common in adults,
affecting nearly 20,000 people each year in the United
States. Brain tumors are also among the most devastating
of human malignancies, affecting the organ that defines
the “self” and thus severely compromising
quality of life. Malignant gliomas of the cerebral
hemispheres in adults are the most common of brain
tumors and are the focus of our laboratory efforts.
Elucidating the molecular basis of glioma formation
may impact both diagnostic and therapeutic aspects
of clinical neuro-oncology. We have demonstrated alterations
characteristic of specific glioma subtypes and grades.
We originally demonstrated that molecular genetic
analysis could be used to define clinicopathologically
relevant subsets of glioblastomas. We have also shown
that molecular genetic alterations are powerful predictors
of chemotherapeutic response and survival in patients
with anaplastic oligodendrogliomas. Those patients
whose anaplastic oligodendrogliomas have 1p loss essentially
always respond to chemotherapy, and those with combined
1p and 19q loss that lack other detectable alterations
have durable responses and long survival times. In
contrast, those whose tumors lack these genetic alterations
but harbor others such as EGFR amplification rarely
respond to chemotherapy in a durable manner and have
short survivals. Hence, genotyping can direct therapeutic
choices for these patients, and is now used in clinical
practice.
To achieve its translational research goals, the
laboratory applies a wide variety of molecular pathology
approaches—such as expression profiling, laser
capture microdissection, tissue microarrays, quantitative
RT-PCR out of paraffin-embedded materials, and array
comparative genomic hybridization on DNA obtained
from paraffin embedded material—to study malignant
gliomas. For example, the group showed that class
prediction models, based on defined expression profiles,
classify diagnostically challenging malignant gliomas
in a manner that better correlates with clinical outcome
than does standard pathology.
The laboratory is also involved in molecular genetic
study of other forms of primary human brain tumors.
In particular, we have studied the genetic basis of
certain inherited neurological tumor syndromes, such
as neurofibromatosis 2. We have also functioned as
a reference laboratory for standard and molecular
pathological analyses, including for the Dana-Farber/Harvard
Cancer Center, for the brain tumor group of the NCI’s
Mouse Models of Human Cancer Consortium, and for ongoing
studies of gene therapy in glioblastomas
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