Methods of analyzing the genome and its expression: medical applications

作者：Le Gall Jean Yves

来源：Bulletin de l Academie Nationale de Medecine, 2012, 196(1): 151-171.

• MASS SPECTROMETRY
• MAGNETIC RESONANCE IMAGING
• BASE SEQUENCE
• COLONIC NEOPLASMS
• RECTAL NEOPLASMS
• MELANOMA
• BREAST NEOPLASMS

Medical biology is rapidly evolving from the study of one or several individual analytes to a more global approach in which the genome and its expression are taken into account as a whole, by means of genomic, transcriptomic or proteomic methods. This report focuses on four such analytical methods (mass spectrometry, nuclear magnetic resonance, DNA sequencing, and DNA chips) and four aspects of oncology, the field in which these methods offers most promise. Nuclear magnetic resonance is restricted to applications in fundamental biology, and particularly structural studies, being relatively slow and poorly sensitive. With new devices and greater computing power, mass spectrometry is finding increasing uses in hospital laboratories, for the analysis of sterols, steroids, bile acids, prostaglandins, glyco- and sphingolipids, etc., detection of SNPs and mutations, high-throughput genotyping, rapid diagnosis of bacterial infections, screening and diagnosis of hereditary diseases, toxicology, etc. Oligonucleotide microarrays, some now reaching a density of 2 500 000 SNPs, are used for genome-wide association studies (GWAS) to identify genetic factors underlying common multifactorial diseases, although the results have so far provened rather disappointing. Results obtained with CGH arrays, using chips bearing large DNA fragments (BAC or PAC), have revealed large scale genomic variations, or copy number variants, involving some 4.8 % of the genome and being implicated in a variety of hereditary and non hereditary disorders. The most impressive developments concern DNA sequencing : new high-throughput technologies will be able to sequence the entire genome in a few hours at near-negligible cost; they are currently used to identify culprit genes in very rare diseases and to characterize genetic anomalies in leukemia and solid tumors. Several international programs are seeking to improve histological classifications, to identify "critical" genes, to identify molecular prognostic indicators and to develop targeted treatments. One example is a selective inhibitor (PLX4032) of the BRAF gene, which is mutated (V600E) in about 50 % of melanomas.

• 出版日期2012-1