Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Basturk, O (Author) Other; Berger, MF (Author) Other; Yamaguchi, H (Author) Other; Adsay, V (Author) Other; Askan, G (Author) Other; Bhanot, UK (Author) Other; Zehir, A (Author) Other; Carneiro F (Author) FMUP; Hong, SM (Author) Other; Zamboni, G (Author) Other; Dikoglu, E (Author) Other; Jobanputra, V (Author) Other; Wrzeszczynski, KO (Author) Other; Balci, S (Author) Other; Allen, P (Author) Other; Ikari, N (Author) Other; Takeuchi, S (Author) Other; Akagawa, H (Author) Other; Kanno, A (Author) Other; Shimosegawa, T (Author) Other; Morikawa, T (Author) Other; Motoi, F (Author) Other; Unno, M (Author) Other; Higuchi, R (Author) Other; Yamamoto, M (Author) Other; Shimizu, K (Author) Other; Furukawa, T (Author) Other; Klimstra, DS (Author) Other

Journal

Title: Modern Pathology

Vol. 30

Pages: 1760-1772

ISSN: 0893-3952

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 34 Citations

Scopus - 41 Citations

Other information

Authenticus ID: P-00N-69C

DOI: 10.1038/modpathol.2017.60

Abstract (EN): Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (>= 300) genes, or whole-exome sequencing. Three of these intraductal tubulopapillary neoplasms were also subjected to whole-genome sequencing. All intraductal tubulopapillary neoplasms revealed the characteristic histologic (cellular intraductal nodules of back-to-back tubular glands lined by predominantly cuboidal cells with atypical nuclei and no obvious intracellular mucin) and immunohistochemical (immunolabeled with MUC1 and MUC6 but were negative for MUC2 and MUC5AC) features. By genomic analyses, there was loss of CDKN2A in 5/20 (25%) of these cases. However, the majority of the previously reported intraductal papillary mucinous neoplasm-related alterations were absent. Moreover, in contrast to most ductal neoplasms of the pancreas, MAP-kinase pathway was not involved. In fact, 2/22 (9%) of intraductal tubulopapillary neoplasms did not reveal any mutations in the tested genes. However, certain chromatin remodeling genes (MLL1, MLL2, MLL3, BAP1, PBRM1, EED, and ATRX) were found to be mutated in 7/22 (32%) of intraductal tubulopapillary neoplasms and 27% harbored phosphatidylinositol 3-kinase (PI3K) pathway (PIK3CA, PIK3CB, INPP4A, and PTEN) mutations. In addition, 4/ 18 (18%) of intraductal tubulopapillary neoplasms had FGFR2 fusions (FGFR2-CEP55, FGFR2-SASS6, DISP1-FGFR2, FGFR2-TXLNA, and FGFR2-VCL) and 1/18 (5.5%) had STRN-ALK fusion. Intraductal tubulopapillary neoplasm is a distinct clinicopathologic entity in the pancreas. Although its intraductal nature and some clinicopathologic features resemble those of intraductal papillary mucinous neoplasm, our results suggest that intraductal tubulopapillary neoplasm has distinguishing genetic characteristics. Some of these mutated genes are potentially targetable. Future functional studies will be needed to determine the consequences of these gene alterations.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13