Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms

Skaro, Michael; Nanda, Neha; Gauthier, Christian; Felsenstein, Matthäus; Jiang, Zhengdong; Qiu, Miaozhen; Shindo, Koji; Yu, Jun; Hutchings, Danielle; Javed, Ammar A.; Beckman, Ross M.; He, Jin; Wolfgang, Christopher L.; Thompson, Elizabeth D.; Hruban, Ralph H.; Klein, Alison P.; Goggins, Michael; Wood, Laura D.; Roberts, Nicholas J.

doi:10.1053/j.gastro.2019.01.254

Cited by 52 publications

(38 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Invasive carcinoma can develop both at the site of the IPMNs and at a different one, which is the main reason why most studies propose a detailed investigation of the entire pancreatic gland, including for remnant pancreas disease after an eventual partial pancreatectomy [ [7] , [8] , [9] ]. These findings associated with molecular studies of IPMNs support the concept of a “field defect” and show evidence that multifocal IPMNs are clonally distinct from each other [ 7 , 12 ].…”

Section: Discussionsupporting

confidence: 55%

“…From a genetic point of view, mutations can be identified and may be related to the increased risk of malignant transformation for a given IPMN, including germline mutations in a pancreatic cancer susceptibility gene: ATM , BRCA2 , MSH6 and PALB2 [ 12 ]. Currently, several panels are available and can contribute to the decision-making process.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mixed-type intraductal papillary mucinous neoplasm: Tailored surgical planning - case report

Bassaneze¹,

Laham²,

Gomes

et al. 2020

International Journal of Surgery Case Reports

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Mixed-type intraductal papillary mucinous neoplasm: Tailored surgical planning - case report

Bassaneze¹,

Laham²,

Gomes

et al. 2020

International Journal of Surgery Case Reports

View full text Add to dashboard Cite

show abstract

“…For example, we identified alterations in the DNA damage response gene ATM in 17% of the analyzed cases. Germline mutations in ATM have been recently reported in patients that developed IPMNs, highlighting the potential importance of this gene in IPMN risk 19 . In addition, mucinous (colloid) carcinomas are significantly more common than typical ductal carcinomas in patients with germline ATM mutations, further highlighting the link between mutations in this gene and IPMNs 20 .…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of malignant progression in neoplastic pancreatic cysts

et al. 2020

Self Cite

View full text Add to dashboard Cite

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention.

show abstract

“…Based on imaging studies, pancreatic cystic neoplasms (PCNs) are being diagnosed with increasing frequency, the prevalence of PCNs in the general population is estimated to be between 2.6% and 45% [1–4]. Clinical differential diagnosis between the potential malignant pancreatic mucinous cystic neoplasm (MCN) and the mostly benign serous cystic neoplasm (SCN) remains challenging [5–8]. According to the Cochrane evidence-based guideline on PCNs, there are no clinical biomarkers of DNA, RNA, or protein in the blood to differentiate PCNs, high-grade dysplasia, or adenocarcinoma [9–12].…”

Section: Introductionmentioning

confidence: 99%

Glycopatterns and Glycoproteins Changes in MCN and SCN: A Prospective Cohort Study

Wang

Sun²,

Feng

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

Background. Advances in imaging improve the detection of malignant pancreatic cystic including mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic adenocarcinoma (MCA), but the distinction between benign and malignant lesions remains a problem. In an effort to establish glycopatterns as potential biomarkers for differential diagnosis between MCN and SCN, we systematically investigated the alterations of glycopatterns in cystic fluids for both SCN and MCN. Methods. Among the 75 patients enrolled, 37 were diagnosed as MCN and 38 as SCN based on histology. Lectin microarray analysis was performed on each sample, and the fluorescence intensity was used to obtain the fold-change. Then, mixed cyst fluids of MCN group and SCN group were cross bonded with magnetic particles coupled by Lectin STL and WGA, respectively. Hydrophilic interaction liquid chromatography (HILIC) enrichment was performed, liquid chromatography (LC)/mass spectrometry (MS) analysis and bioinformatical analysis was conducted to find the differential glycoproteins between MCNs and SCNs. Results. Through analysis of lectin microarray between MCNs and SCNs, stronger lectin signal patterns were assigned to Lectin WFA, DBA, STL, WGA, and BPL; and weaker signal patterns were assigned to Lectin PTL-I, Con A, ACA, and MAL-I. The glycoproteins were enriched by STL or WGA-coupled magnetic particles. Furthermore, the 10 identified correspondding genes were found to be significantly elevated in the mucinous cystadenoma: CLU, A2M, FGA, FGB, FGG, PLG, SERPINA1, SERPING1, C5, C8A, and C9. Bioinformatics analysis revealed that the above genes may activate the KEGG pathway: immune complement system. Conclusion. This study shows changes in glycopatterns and glycoproteins are associated with MCNs and SCNs.

show abstract

Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms

Abstract: Background & aims-Many patients with pancreatic adenocarcinoma (PDAC) carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal

Cited by 52 publications

References 61 publications

Mixed-type intraductal papillary mucinous neoplasm: Tailored surgical planning - case report

Mixed-type intraductal papillary mucinous neoplasm: Tailored surgical planning - case report

Genomic characterization of malignant progression in neoplastic pancreatic cysts

Glycopatterns and Glycoproteins Changes in MCN and SCN: A Prospective Cohort Study

Contact Info

Product

Resources

About