A 6-gene signature identifies four molecular subgroups of neuroblastoma

• Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p

Nyckelord

TUMOR-SUPPRESSOR GENE

COPY NUMBER

ACTIVATING MUTATIONS

MESSENGER-RNA

ACUTE LYMPHOBLASTIC-LEUKEMIA

ONCOLOGY GROUP

EXPRESSION-BASED CLASSIFICATION

ALK KINASE

PROGRESSION

AMPLIFICATION

EXPRESSION-BASED CLASSIFICATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR GENE; ACTIVATING MUTATIONS; ONCOLOGY GROUP; MESSENGER-RNA; COPY scigloo.NUMBER; ALK KINASE; AMPLIFICATION; PROGRESSION

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