Molecular profiling of pancreatic neuroendocrine tumors in sporadic and Von Hippel-Lindau patients.

نویسندگان

  • Daniela Speisky
  • Aurélie Duces
  • Ivan Bièche
  • Vinciane Rebours
  • Pascal Hammel
  • Alain Sauvanet
  • Stéphane Richard
  • Pierre Bedossa
  • Michel Vidaud
  • Arnaud Murat
  • Patricia Niccoli
  • Jean-Yves Scoazec
  • Philippe Ruszniewski
  • Anne Couvelard
چکیده

PURPOSE Von Hippel-Lindau (VHL) disease is an inherited syndrome caused by germline mutations in the VHL tumor suppressor gene, predisposing to a variety of neoplasms including pancreatic neuroendocrine tumors (PanNET). In VHL disease, PanNET probably progress according to a specific pathway of carcinogenesis. Our aim was to characterize by molecular quantitative analysis a panel of molecules implicated in the VHL pathway and in tumor progression in the PanNET of patients with VHL. EXPERIMENTAL DESIGN The expression of 52 genes was studied by quantitative reverse transcriptase PCR in 18 patients with VHL operated on for PanNET and compared with 16 non-VHL PanNET. The VHL and non-VHL tumors were matched according to their size and cell proliferation. For some genes, we looked for differences in the protein expression in VHL PanNET (n = 31), microadenomas (n = 22), and non-VHL PanNET (n = 16), included in tissue microarray blocks. RESULTS Nineteen (36%) genes were significantly upregulated and three (6%) downregulated in VHL PanNET. The upregulated genes were related to (i) hypoxia-inducible factor (HIF) molecules (CA9, HIF2A, and GLUT1), (ii) angiogenesis (CDH5, VEGFR1, EDNRA, ANGPT2, CD34, VEGFR2, VEGFA, and ANGPT1), (iii) the processes of epithelial-mesenchymal transition (VIM) and/or metastasis (LAMA4 and CXCR4), (iv) growth factors and receptors (PDGFB, IRS1, and ERBB1), or (v) cell cycle (CCND1 and CDKN2A). The downregulated genes were related to (i) EMT (OCLN) and (ii) signaling pathways (RPS6KB1 and GADD45B). CONCLUSION This study shows that the progression of PanNET in patients with VHL tumors follows a specific pathway and supports that targeting molecules specifically involved may be of therapeutic importance.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Bilateral pheochromocytoma as first manifestation of von Hippel-Lindau disease: a case report.

Von Hippel-Lindau syndrome is an autosomal dominant disorder that includes susceptibility to hemangioblastomas of the eyes and central nervous system, renal clear cell carcinoma, multiple pancreatic cysts, serous cystadenomas and pancreatic neuroendocrine tumors, pheochromocytoma, endolymphatic sac tumors, and cystadenomas of the epididymis and broad ligament. We present a 16-year-old male who ...

متن کامل

Propranolol Decreases the Viability and Triggers Apoptosis in Hemangioblastoma Cells from Von Hippel-Lindau Patients

Von Hippel-Lindau (VHL) disease is a rare type of oncological disease with an incidence of 1/36,000 individuals in the general population [1,2]. The most frequent tumors are hemangioblastomas (HB) of the central nervous system (CNS) and retina, as well as renal cell carcinoma [3,4]. In addition, pheochromocytomas, pancreatic neuroendocrine tumors, pancreatic serous cystoadenomas, endolymphatic ...

متن کامل

Laparoscopic Surgical Treatment of Neuroendocrine Pancreatic Tumors

Pancreatic Endocrine Tumors (PNETs) represent a rare, but important subset of pancreatic neoplasms. These tumors account for 2–4% of all clinically detected pancreatic tumors. Their overall incidence is approximately 1 of 100 000 people per year [1,2]. PNETs consist of single or multiple benign or malignant neoplasms and are associated with multiple endocrine neoplasia type 1 (MEN1) in 10– 20% ...

متن کامل

Late recurrence after surgical resection of a pancreatic tumor in von Hippel-Lindau disease.

CONTEXT Patients with von Hippel-Lindau syndrome, a dominantly inherited familial cancer syndrome, develop a variety of tumors in different organ systems which make the clinical management of these patients complex. CASE REPORT The long clinical history of a 45-year-old woman started at 22 years of age when she had surgery for a right adrenal pheochromocytoma. Two years later, a pancreaticodu...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 18 10  شماره 

صفحات  -

تاریخ انتشار 2012