Genetic and molecular alterations in rhabdomyosarcoma: mRNA overexpression of MCL1 and MAP2K4 genes.
Rhabdomyosarcoma, the most common soft tissue sarcoma in childhood, belongs to the small round cell tumor family and is classified according to its histopathological features as embryonal, alveolar and pleomorphic. In this study we propose to explore genetic alterations involved in rhabdomyosarcoma tumorigenesis and assess the level of mRNA gene expression of controlling survival signalling pathways. For genetic and molecular analysis, array-based comparative genomic hybridization, combined with Real Time PCR using the comparative method, was performed on 14 primary well-characterized human primary rhabdomyosarcomas. Multiple changes affecting chromosome arms were detected in all cases, including gain or loss of specific regions harbouring cancer progression-associated genes. Evaluation of mRNA levels showed in the majority of cases overexpression of MCL1 and MAP2K4 genes, both involved in cell viability regulation. Our findings on rhabdomyosarcoma samples showed multiple copy number alterations in chromosome regions implicated in malignancy progression and indicated a strong expression of MAP2K4 and MCL1 genes, both involved in different biological functions of complicated signalling pathways.
Pazzaglia
L
L
Laboratory of Oncologic Research, Rizzoli Orthopaedic Institute, Bologna, Italy. laura.pazzaglia@ior.it
Chiechi
A
A
Conti
A
A
Gamberi
G
G
Magagnoli
G
G
Novello
C
C
Morandi
L
L
Picci
P
P
Mercuri
M
M
Benassi
M S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000235:genetics*
D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human