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Application of advances in molecular biology to the treatment of brain tumors

Current Oncology Reports (Impact Factor: 3.33). 04/2012; 2(5):425-433. DOI:10.1007/s11912-000-0062-4

ABSTRACT Recent advances in molecular biology have substantially improved our understanding of the molecular genetics of primary brain
neoplasms. Soon each histopathologic category of glioma will be further divided into subgroups according to similar genetic
background, gene expression profile, and similarity of biologic responses to radiotherapy or chemotherapy. Identification
of key molecules that are specifically altered in neoplastic cells will provide candidate molecular targets for tumor treatment.
Novel therapeutic tools for targeting tumor cells, such as viral vectors for gene therapy, have been created. In the near
future, the accumulation of new knowledge in brain tumor biology and genetics, combined with rational drug design, will revolutionize
the treatment of malignant gliomas, which are among the most lethal human cancers.

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    ABSTRACT: Molecular anatomic pathology represents the blend of traditional morphological methods and the multigene approach to determine cancer-related gene alterations for diagnostic and prognostic purposes. Microdissection genotyping was utilized to characterize 197 gliomas with targeted microdissection of 2–7 areas spanning the spectrum of histologic types and grades. The methodology described herein is complementary to the existing realities of pathology practice. The technique utilizes paraffin-embedded fixative-treated tissue of small sample size after the primary morphological examination by the pathologist. Molecular information derived from microdissection genotyping in combination with the traditional histological information, results in an enhanced understanding of glioma formation and biological progression leading to improvements in diagnosis and prediction of prognosis. In all, 100% or 32 of 32 cases with at least partial treatment response was observed in neoplasms possessing the 1p or 1p/19q loss. The 19q loss alone without coexisting 1p showed no improvement in treatment response. Gliomas lacking 1p loss with only allelic loss involving 3p, 5q, 9p, 10q and 17p showed unfavorable outcome of only 35%, or six of 17 cases with treatment response. In addition, the determination of fractional allelic loss (favorable/unfavorable), was a very good independent predictor of biological behavior. These findings emphasize the importance of determining the cumulative pattern of mutational damage on 16 distinct sites or more, especially in the presence of 1p loss which in isolation or in combination with 19q is a favorable prognostic factor for therapeutic response.Keywords: microdissection genotyping, molecular anatomic pathology, glioma, loss of heterozygosity, fractional allelic loss, 1p/19q
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