title: Molecular classification of amyotrophic lateral sclerosis by unsupervised clustering of gene expression in motor cortex.
abstract: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, caused by the loss of motor neurons in the brain and spinal cord. Although 10% of ALS cases are familial (FALS), the majority are sporadic (SALS) and probably associated to a multifactorial etiology. Currently there is no cure or prevention for ALS. A prerequisite to formulating therapeutic strategies is gaining understanding of its etio-pathogenic mechanisms. In this study we analyzed whole-genome expression profiles of 41 motor cortex samples of control (10) and sporadic ALS (31) patients. Unsupervised hierarchical clustering was able to separate control from SALS patients. In addition, SALS patients were subdivided in two different groups that were associated to different deregulated pathways and genes, some of which were previously associated to familiar ALS. These experiments are the first to highlight the genomic heterogeneity of sporadic ALS and reveal new clues to its pathogenesis and potential therapeutic targets.
authors.affiliation: Department of (Neuro) Pathology, Academic Medical Center, Amsterdam, The Netherlands; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Department of Neurogenetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.affiliation: Department of (Neuro) Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Anand
authors.initials: A
authors.lastname: Iyer
authors.affiliation: Department of Neurogenetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Anneloor L M A
authors.initials: AL
authors.lastname: ten Asbroek
authors.affiliation: Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Morello
authors.affiliation: Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Catania, Italy. Electronic address: sebastiano.cavallaro@cnr.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cavallaro
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000145:classification* / Q000378:metabolism*; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000069558:Unsupervised Machine Learning; D044465:White People
chemical_list: D012333:RNA, Messenger
keywords: ALS; Molecular taxonomy; Pathway; Transcriptomics