Medicine • Clinical Research • Clinical Trials • Molecular Biology • Pancreatic Cancer • Pancreatic Cystic Neoplasms • Cancer Genomics • General Surgery • Hepatobiliary Surgery • Translational Research • Education
Languages
English • Italian
Interests
Traveling • New Technologies • Guitar Playing • Skiing
University of Maryland Medical Center
General Surgery Resident
Johns Hopkins Hospital 2013 - Jun 2016
Post-Doctoral Fellow
Education:
Università Degli Studi Di Verona 2008 - 2014
Università Degli Studi Di Verona 2001 - 2007
Doctor of Medicine, Doctorates, Medicine
Skills:
Medicine Clinical Research Clinical Trials Molecular Biology Pancreatic Cancer Pancreatic Cystic Neoplasms Cancer Genomics General Surgery Hepatobiliary Surgery Translational Research Education
- Baltimore MD, US Kenneth W. Kinzler - Baltimore MD, US Nickolas Papadopoulos - Towson MD, US Jian Wu - Baltimore MD, US Ralph Hruban - Baltimore MD, US Anirban Maitra - Baltimore MD, US Marco Dal Molin - Baltimore MD, US
Assignee:
The Johns Hopkins University - Baltimore MD
International Classification:
C12Q 1/6886 C12Q 1/6883
Abstract:
More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations, but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.
- Baltimore MD, US Kenneth W. Kinzler - Baltimore MD, US Nickolas Papadopoulos - Towson MD, US Jian Wu - Baltimore MD, US Ralph Hruban - Baltimore MD, US Anirban Maitra - Baltimore MD, US Marco Dal Molin - Baltimore MD, US
International Classification:
C12Q 1/68
US Classification:
506 9, 536 2431, 435 612, 506 16, 435 611
Abstract:
More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations, but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.