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GNAS sequencing identifies IPMN-specific mutations in a subgroup of diminutive pancreatic cysts referred to as "incipient IPMNs".
Am J Surg Pathol 2014; 38(3):360-3AJ

Abstract

Incipient intraductal papillary mucinous neoplasms (IPMNs) are poorly described subcentimeter pancreatic cysts with papillae and mucin similar to IPMNs. They are larger than pancreatic intraepithelial neoplasia but do not meet the cutoff size for IPMNs (≥ 1 cm). GNAS codon 201 mutations are hallmark genetic alterations of IPMNs. Hence, we sought to determine the GNAS status of incipient IPMNs to better classify these lesions. Incipient IPMNs from 3 institutions were histologically reassessed, manually microdissected, and the genomic DNA was extracted. Using a sensitive digital ligation technique, the mutational status of KRAS at codon 12 and GNAS at codon 201 was determined. We included 21 incipient IPMNs from 7 male and 12 female patients with a median age of 63 years (range, 40 to 76 y). Most patients underwent surgery for pancreatic ductal adenocarcinoma (N = 8) or ampullary adenocarcinoma (N = 3). The median incipient IPMN size was 4 mm (range, 2 to 7 mm), and a majority had gastric-foveolar (N = 11) or intestinal (N = 5) differentiation. The maximum dysplasia observed was intermediate, and most of the lesions had intermediate-grade dysplasia. Mutational analysis revealed KRAS codon 12 mutations in all 21 incipient IPMNs, whereas 7 lesions (33%) in 7 individual patients harbored GNAS codon 201 mutations. The presence of GNAS 201 mutations in incipient IPMNs suggests that a fraction of these cysts are in fact small IPMNs. Morphologically, incipient IPMNs do not appear to be high-risk lesions. Additional studies in a larger cohort are needed to define the relationship of incipient IPMNs to larger IPMNs and, more importantly, to determine their clinical significance.

Authors+Show Affiliations

Departments of *Pathology ††Oncology #Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine ‡Ludwig Center for Cancer Genetics **Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD §Department of Pathology, Microbiology, Immunology, Vanderbilt University Medical Center, Nashville, TN Departments of †General, Visceral, Thoracic and Vascular Surgery ¶Prostate Cancer Research ∥Institute of Pathology, University of Bonn, Bonn, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24525507

Citation

Matthaei, Hanno, et al. "GNAS Sequencing Identifies IPMN-specific Mutations in a Subgroup of Diminutive Pancreatic Cysts Referred to as "incipient IPMNs"." The American Journal of Surgical Pathology, vol. 38, no. 3, 2014, pp. 360-3.
Matthaei H, Wu J, Dal Molin M, et al. GNAS sequencing identifies IPMN-specific mutations in a subgroup of diminutive pancreatic cysts referred to as "incipient IPMNs". Am J Surg Pathol. 2014;38(3):360-3.
Matthaei, H., Wu, J., Dal Molin, M., Shi, C., Perner, S., Kristiansen, G., ... Hruban, R. H. (2014). GNAS sequencing identifies IPMN-specific mutations in a subgroup of diminutive pancreatic cysts referred to as "incipient IPMNs". The American Journal of Surgical Pathology, 38(3), pp. 360-3. doi:10.1097/PAS.0000000000000117.
Matthaei H, et al. GNAS Sequencing Identifies IPMN-specific Mutations in a Subgroup of Diminutive Pancreatic Cysts Referred to as "incipient IPMNs". Am J Surg Pathol. 2014;38(3):360-3. PubMed PMID: 24525507.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GNAS sequencing identifies IPMN-specific mutations in a subgroup of diminutive pancreatic cysts referred to as "incipient IPMNs". AU - Matthaei,Hanno, AU - Wu,Jian, AU - Dal Molin,Marco, AU - Shi,Chanjuan, AU - Perner,Sven, AU - Kristiansen,Glen, AU - Lingohr,Philipp, AU - Kalff,Jörg C, AU - Wolfgang,Christopher L, AU - Kinzler,Kenneth W, AU - Vogelstein,Bert, AU - Maitra,Anirban, AU - Hruban,Ralph H, PY - 2014/2/15/entrez PY - 2014/2/15/pubmed PY - 2014/4/11/medline SP - 360 EP - 3 JF - The American journal of surgical pathology JO - Am. J. Surg. Pathol. VL - 38 IS - 3 N2 - Incipient intraductal papillary mucinous neoplasms (IPMNs) are poorly described subcentimeter pancreatic cysts with papillae and mucin similar to IPMNs. They are larger than pancreatic intraepithelial neoplasia but do not meet the cutoff size for IPMNs (≥ 1 cm). GNAS codon 201 mutations are hallmark genetic alterations of IPMNs. Hence, we sought to determine the GNAS status of incipient IPMNs to better classify these lesions. Incipient IPMNs from 3 institutions were histologically reassessed, manually microdissected, and the genomic DNA was extracted. Using a sensitive digital ligation technique, the mutational status of KRAS at codon 12 and GNAS at codon 201 was determined. We included 21 incipient IPMNs from 7 male and 12 female patients with a median age of 63 years (range, 40 to 76 y). Most patients underwent surgery for pancreatic ductal adenocarcinoma (N = 8) or ampullary adenocarcinoma (N = 3). The median incipient IPMN size was 4 mm (range, 2 to 7 mm), and a majority had gastric-foveolar (N = 11) or intestinal (N = 5) differentiation. The maximum dysplasia observed was intermediate, and most of the lesions had intermediate-grade dysplasia. Mutational analysis revealed KRAS codon 12 mutations in all 21 incipient IPMNs, whereas 7 lesions (33%) in 7 individual patients harbored GNAS codon 201 mutations. The presence of GNAS 201 mutations in incipient IPMNs suggests that a fraction of these cysts are in fact small IPMNs. Morphologically, incipient IPMNs do not appear to be high-risk lesions. Additional studies in a larger cohort are needed to define the relationship of incipient IPMNs to larger IPMNs and, more importantly, to determine their clinical significance. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/24525507/GNAS_sequencing_identifies_IPMN_specific_mutations_in_a_subgroup_of_diminutive_pancreatic_cysts_referred_to_as_"incipient_IPMNs"_ L2 - http://Insights.ovid.com/pubmed?pmid=24525507 DB - PRIME DP - Unbound Medicine ER -