Serine hydroxymethyltransferase 2 expression promotes tumorigenesis in rhabdomyosarcoma with 12q13-q14 amplification

التفاصيل البيبلوغرافية
العنوان: Serine hydroxymethyltransferase 2 expression promotes tumorigenesis in rhabdomyosarcoma with 12q13-q14 amplification
المؤلفون: Prasantha L. Vemu, Javed Khan, Bishwanath Chatterjee, Wenyue Sun, Thanh Hung Nguyen, Jack F. Shern, Gregory E. Hoy, Salah Boudjadi, Frederic G. Barr
المصدر: J Clin Invest
بيانات النشر: American Society for Clinical Investigation, 2021.
سنة النشر: 2021
مصطلحات موضوعية: Male, musculoskeletal diseases, genetic structures, Carcinogenesis, Biology, medicine.disease_cause, Gene Expression Regulation, Enzymologic, Rhabdomyosarcoma, medicine, Humans, Glycine Hydroxymethyltransferase, Gene knockdown, Chromosomes, Human, Pair 12, General Medicine, Amplicon, medicine.disease, eye diseases, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Cell culture, Serine hydroxymethyltransferase, Chromosomal region, Cancer research, Adenocarcinoma, Female, human activities, Research Article
الوصف: The 12q13-q14 chromosomal region is recurrently amplified in 25% of fusion-positive (FP) rhabdomyosarcoma (RMS) cases and is associated with a poor prognosis. To identify amplified oncogenes in FP RMS, we compared the size, gene composition, and expression of 12q13-q14 amplicons in FP RMS with those of other cancer categories (glioblastoma multiforme, lung adenocarcinoma, and liposarcoma) in which 12q13-q14 amplification frequently occurs. We uncovered a 0.2 Mb region that is commonly amplified across these cancers and includes CDK4 and 6 other genes that are overexpressed in amplicon-positive samples. Additionally, we identified a 0.5 Mb segment that is only recurrently amplified in FP RMS and includes 4 genes that are overexpressed in amplicon-positive RMS. Among these genes, only serine hydroxymethyltransferase 2 (SHMT2) was overexpressed at the protein level in an amplicon-positive RMS cell line. SHMT2 knockdown in amplicon-positive RMS cells suppressed growth, transformation, and tumorigenesis, whereas overexpression in amplicon-negative RMS cells promoted these phenotypes. High SHMT2 expression reduced sensitivity of FP RMS cells to SHIN1, a direct SHMT2 inhibitor, but sensitized cells to pemetrexed, an inhibitor of the folate cycle. In conclusion, our study demonstrates that SHMT2 contributes to tumorigenesis in FP RMS and that SHMT2 amplification predicts differential response to drugs targeting this metabolic pathway.
تدمد: 1558-8238
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c69b4b5425e48d3e7b7e08d0f4cc5e29Test
https://doi.org/10.1172/jci138022Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....c69b4b5425e48d3e7b7e08d0f4cc5e29
قاعدة البيانات: OpenAIRE