Details

Autor(en) / Beteiligte

• Gadd, Samantha
• Beezhold, Patricia
• Jennings, Lawrence
• George, David
• Leuer, Katrin
• Huang, Chiang-Ching
• Huff, Vicki
• Tognon, Cristina
• Sorensen, Poul HB
• Triche, Timothy
• Coffin, Cheryl M
• Perlman, Elizabeth J

Titel

Mediators of receptor tyrosine kinase activation in infantile fibrosarcoma: a Children's Oncology Group study

Ist Teil von

• The Journal of pathology, 2012-09, Vol.228 (1), p.119-130

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2012

Quelle

Access via Wiley Online Library

Beschreibungen/Notizen

• Infantile fibrosarcoma (IFS; also known as cellular congenital mesoblastic nephroma, CMN, when in the kidney) is a rare, undifferentiated tumour often characterized by the ETV6‐NTRK3 fusion transcript. Our goal was to identify downstream pathways, diagnostic markers and potential therapeutic targets for IFS/CMN. Global gene expression, reverse‐phase protein array and ETV6‐NTRK3 fusion analyses were performed on 14 IFS/CMN and compared with 41 other paediatric renal tumours. These analyses confirm significant receptor tyrosine kinase (RTK) activation, with evidence of PI3‐Akt, MAPK and SRC activation. In particular, GAB2 docking protein, STAT5‐pTyr‐694, STAT3‐pSer‐729 and YAP‐pSer‐127 were elevated, and TAZ‐pSer‐89 was decreased. This provides mRNA and proteomic evidence that GAB2, STAT activation and phosphorylation of the Hippo pathway transcription co‐activators YAP and TAZ contribute to the RTK signal transduction in IFS/CMN. All IFS/CMN tumours displayed a distinctive gene expression pattern that may be diagnostically useful. Unexpectedly, abundant ETV6‐NTRK3 transcript copies were present in only 7/14 IFS, with very low copy number in 3/14. An additional 4/14 were negative by RT‐PCR and absence of ETV6‐NTRK3 was confirmed by FISH for both ETV6 and NTRK3. Therefore, molecular mechanisms other than ETV6‐NTRK3 fusion are responsible for the development of some IFS/CMNs and the absence of ETV6‐NTRK3 fusion products should not exclude IFS/CMN as a diagnosis. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.