TY - JOUR
T1 - Anaplastic lymphoma kinase aberrations correlate with metastatic features in pediatric rhabdomyosarcoma
AU - Gasparini, Patrizia
AU - Casanova, Michela
AU - Villa, Raffaella
AU - Collini, Paola
AU - Alaggio, Rita
AU - Zin, Angelica
AU - Bonvini, Paolo
AU - Antonescu, Cristina R.
AU - Boldrini, Renata
AU - Caserini, Roberto
AU - Moro, Massimo
AU - Centonze, Giovanni
AU - Meazza, Cristina
AU - Massimino, Maura
AU - Bergamaschi, Luca
AU - Luksch, Roberto
AU - Chiaravalli, Stefano
AU - Bisogno, Gianni
AU - Zaffaroni, Nadia
AU - Daidone, Maria Grazia
AU - Sozzi, Gabriella
AU - Ferrari, Andrea
PY - 2016
Y1 - 2016
N2 - Rhabdomyosarcoma (RMS) is the most frequent soft tissue tumor in childhood and arises from immature mesenchymal cells committed to skeletal muscle differentiation. Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in several cancers. Moreover, ALK full-length receptor protein has been observed in RMS, although its clinical and functional significance is yet controversial. The role of ALK and its clinical relevance were investigated in a selected cohort of 74 FFPE pediatric RMS and a panel of RMS cell lines, evaluating its gene and protein status, utilizing Fluorescent In Situ Hybridization (FISH), immunohistochemistry (IHC) and Western blot approaches. Moreover, to get insight into its possible therapeutic relevance, effects of ALK silencing on cell proliferation, invasion and apoptosis were studied in RMS cells. ALK IHC positivity was significantly correlated with gene copy number gain, the alveolar subtype, PAX3/7-FOXO1 rearrangements, the presence of metastasis at diagnosis and a worse overall outcome. Furthermore, EML4-ALK fusion gene associated with higher protein expression was identified in an embryonal RMS. ALK silencing in RH30 ALK positive cells strongly inhibited invasion capability. Overall, our data suggest a potential role of ALK in pediatric RMS.
AB - Rhabdomyosarcoma (RMS) is the most frequent soft tissue tumor in childhood and arises from immature mesenchymal cells committed to skeletal muscle differentiation. Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in several cancers. Moreover, ALK full-length receptor protein has been observed in RMS, although its clinical and functional significance is yet controversial. The role of ALK and its clinical relevance were investigated in a selected cohort of 74 FFPE pediatric RMS and a panel of RMS cell lines, evaluating its gene and protein status, utilizing Fluorescent In Situ Hybridization (FISH), immunohistochemistry (IHC) and Western blot approaches. Moreover, to get insight into its possible therapeutic relevance, effects of ALK silencing on cell proliferation, invasion and apoptosis were studied in RMS cells. ALK IHC positivity was significantly correlated with gene copy number gain, the alveolar subtype, PAX3/7-FOXO1 rearrangements, the presence of metastasis at diagnosis and a worse overall outcome. Furthermore, EML4-ALK fusion gene associated with higher protein expression was identified in an embryonal RMS. ALK silencing in RH30 ALK positive cells strongly inhibited invasion capability. Overall, our data suggest a potential role of ALK in pediatric RMS.
KW - Anaplastic lymphoma kinase
KW - Chromosomal rearrangement
KW - EML4-ALK
KW - Metastasis
KW - Rhabdomyosarcoma
UR - http://www.scopus.com/inward/record.url?scp=84991392572&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991392572&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.10368
DO - 10.18632/oncotarget.10368
M3 - Article
AN - SCOPUS:84991392572
VL - 7
SP - 58903
EP - 58914
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 37
ER -