Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pleuropulmonary blastoma (PPB) is a rare malignant intrathoracic tumor primarily affecting children under 5 years of age. PPBs are histologically divided into 3 subtypes: Type 1 PPBs are composed of multiple cysts, and type 3 is a solid lesion with a variable morphologic appearance. Type 2 has a mixed morphology consisting of cystic and solid areas. The genetics of PPB are poorly understood. We analyzed 16 cases of the Kiel Paediatric Tumor Registry with the diagnosis of PPB by comparative genomic hybridization and confirmed some genetic changes by fluorescence in situ hybridization. Furthermore, we performed immunohistochemistry to evaluate insulin-like growth factor type 1 (IGF1R) protein expression. Frequent findings by comparative genomic hybridization were losses on 4q, 5q, 9p and gains on chromosome 8, 17, and 20q. Genomic amplification was observed in 5 cases, 4 related to 15q25qter and 1 to 1p. Fluorescence in situ hybridization could confirm 7 gains of chromosome 8 (7/16, 44%) and 4 amplifications of the IGF1R-gene on 15q26 (4/16, 25%). All of the tumors with IGF1R amplification were type 3 PPBs. One of the PPBs with gain of chromosome 8 was a type 2 tumor and 6 tumors were type 3 PPBs. All but one PPB showed an IGF1R expression by immunohistochemistry. In our series of 16 PPBs, 25% of the tumors have an amplification of the IGF1R gene and 44% show a gain of chromosome 8. All of the tumors with IGF1R amplification were PPBs type 3, indicating that it is a later event in tumor progression, while the gain of chromosome 8 was found in both type 2 and type 3 tumors indicating that these changes are probably earlier events in tumor development. Furthermore, the strong IGF1R protein expression could be a possible therapeutic target in refractory chemoresistant PPBs.
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PMID:Strong Expression and Amplification of IGF1R in Pleuropulmonary Blastomas. 2838 40

Pleuropulmonary blastoma (PPB) is a very rare pediatric lung disease. It can progress from abnormal epithelial cysts to an aggressive sarcoma with poor survival. PPB diagnosis is difficult as it can be confounded with other cystic lung disorders like congenital pulmonary airway malformations (CPAM). PPB is associated with mutations in DICER1 that perturb the microRNA (miRNA) profile in lung. How DICER1 and miRNAs act during PPB pathogenesis remains unsolved. Lung epithelial deletion of the Yin Yang1 (Yy1) gene in mice causes a phenotype mimicking the cystic form of PPB and it affects the expression of key regulators of lung development. Similar changes in expression were observed in PPB but not in CPAM lung biopsies, revealing a distinctive PPB molecular signature. Deregulation of molecules promoting epithelial-mesenchymal transition (EMT) was detected in PPB specimens suggesting that EMT might participate in tumor progression. Changes in miRNA expression also occurred in PPB lung biopsies. miR-125a-3p, a candidate to regulate YY1 expression and lung branching, was abnormally highly expressed in PPB samples. Together, these findings support the concept that reduced expression of YY1, due to the abnormal miRNA profile ensuing DICER1 mutations, contributes to PPB development via its impact on the expression of key lung developmental genes.
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PMID:Deletion of Yy1 in mouse lung epithelium unveils molecular mechanisms governing pleuropulmonary blastoma pathogenesis. 3315 35