التفاصيل البيبلوغرافية
| العنوان: |
Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations |
| المؤلفون: |
Brouillard, Pascal, Schlögel, Matthieu M.J., Homayun Sepehr, Nassim, Helaers, Raphaël, Queisser, Angela, Fastré, Elodie, Boutry, Simon, Schmitz, S., Clapuyt, Philippe, Hammer, Frank, Dompmartin, A., Weitz-Tuoretmaa, Annamaria, Laranne, Jussi, Pasquesoone, Louise, Vilain, Catheline, Boon, Laurence Myriam, Vikkula, Mikka |
| المصدر: |
Orphanet journal of rare diseases, 16 (1 |
| سنة النشر: |
2021 |
| المجموعة: |
DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
| مصطلحات موضوعية: |
Génétique clinique, Pharmacologie, Sciences bio-médicales et agricoles, Allele, Epidemiology, Frequency, Gene, Isolated, Lymphatic malformation, Mutation, PI3K, Somatic, Theragnostic |
| الوصف: |
Background: Theragnostic management, treatment according to precise pathological molecular targets, requests to unravel patients’ genotypes. We used targeted next-generation sequencing (NGS) or digital droplet polymerase chain reaction (ddPCR) to screen for somatic PIK3CA mutations on DNA extracted from resected lesional tissue or lymphatic endothelial cells (LECs) isolated from lesions. Our cohort (n = 143) was composed of unrelated patients suffering from a common lymphatic malformation (LM), a combined lymphatic malformation [lymphatico-venous malformation (LVM), capillaro-lymphatic malformation (CLM), capillaro-lymphatico-venous malformation (CLVM)], or a syndrome [CLVM with hypertrophy (Klippel-Trenaunay-Weber syndrome, KTS), congenital lipomatous overgrowth-vascular malformations-epidermal nevi -syndrome (CLOVES), unclassified PIK3CA-related overgrowth syndrome (PROS) or unclassified vascular (lymphatic) anomaly syndrome (UVA)]. Results: We identified a somatic PIK3CA mutation in resected lesions of 108 out of 143 patients (75.5%). The frequency of the variant allele ranged from 0.54 to 25.33% in tissues, and up to 47% in isolated endothelial cells. We detected a statistically significant difference in the distribution of mutations between patients with common and combined LM compared to the syndromes, but not with KTS. Moreover, the variant allele frequency was higher in the syndromes. Conclusions: Most patients with an common or combined lymphatic malformation with or without overgrowth harbour a somatic PIK3CA mutation. However, in about a quarter of patients, no such mutation was detected, suggesting the existence of (an)other cause(s). We detected a hotspot mutation more frequently in common and combined LMs compared to syndromic cases (CLOVES and PROS). Diagnostic genotyping should thus not be limited to PIK3CA hotspot mutations. Moreover, the higher mutant allele frequency in syndromes suggests a wider distribution in patients’ tissues, facilitating detection. Clinical trials have demonstrated ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
1 full-text file(s): application/pdf |
| اللغة: |
English |
| العلاقة: |
uri/info:doi/10.1186/s13023-021-01898-y; uri/info:pmid/34112235; uri/info:scp/85107823561; https://dipot.ulb.ac.be/dspace/bitstream/2013/326817/1/doi_310461.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/326817Test |
| الإتاحة: |
http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/326817Test |
| رقم الانضمام: |
edsbas.CBFA8172 |
| قاعدة البيانات: |
BASE |
