Academic Journal
Molecular characteristics of early‐onset pancreatic ductal adenocarcinoma
| العنوان: | Molecular characteristics of early‐onset pancreatic ductal adenocarcinoma |
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| المؤلفون: | Silvana Debernardi, Lukasz Liszka, Chara Ntala, Katja Steiger, Irene Esposito, Emanuela Carlotti, Ann‐Marie Baker, Stuart McDonald, Trevor Graham, Branko Dmitrovic, Roger M. Feakins, Tatjana Crnogorac‐Jurcevic |
| المصدر: | Molecular Oncology, Vol 18, Iss 3, Pp 677-690 (2024) |
| بيانات النشر: | Wiley, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | early onset pancreatic cancer, KRAS, p16, p53, SMAD4, tumour heterogeneity, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | The median age of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis is 71 years; however, around 10% present with early‐onset pancreatic cancer (EOPC), i.e., before age 50. The molecular mechanisms underlying such an early onset are unknown. We assessed the role of common PDAC drivers (KRAS, TP53, CDKN2A and SMAD4) and determined their mutational status and protein expression in 90 formalin‐fixed, paraffin‐embedded tissues, including multiple primary and matched metastases, from 37 EOPC patients. KRAS was mutated in 88% of patients; p53 was altered in 94%, and p16 and SMAD4 were lost in 86% and 71% of patients, respectively. Meta‐synthesis showed a higher rate of p53 alterations in EOPC than in late‐onset PDAC (94% vs. 69%, P = 0.0009) and significantly higher loss of SMAD4 (71% vs. 44%, P = 0.0025). The majority of EOPC patients accumulated aberrations in all four drivers; in addition, high tumour heterogeneity was observed across all tissues. The cumulative effect of an exceptionally high rate of alterations in all common PDAC driver genes combined with high tumour heterogeneity suggests an important mechanism underlying the early onset of PDAC. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 |
| Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
| DOI: | 10.1002/1878-0261.13576 |
| URL الوصول: | https://doaj.org/article/28e44b0fd78246999dcb6ae2e2fb819c |
| رقم الانضمام: | edsdoj.28e44b0fd78246999dcb6ae2e2fb819c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.13576 |