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GNAS mutation is a frequent event in pancreatic intraductal papillary mucinous neoplasms and associated adenocarcinomas

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Abstract

In contrast to pancreatic ductal adenocarcinomas (PDAs), intraductal papillary mucinous neoplasms (IPMNs) frequently harbour GNAS mutations. To characterise GNAS-mutated pancreatic carcinomas, we examined mutations of GNAS and KRAS in 290 pancreatic adenocarcinomas and 77 pancreatic intraepithelial neoplasias (PanINs). In 64 % (39/61) of IPMNs and 37 % (11/30) of IPMN-associated adenocarcinomas, a GNAS mutation was found. GNAS mutations were frequent (78 %, 7/9) in mucinous carcinomas, with or without associated IPMN. In contrast, GNAS mutations were rarely observed in PDAs (1 %, 1/88) and PanINs (3 %, 2/77), and not at all in mucinous cystic neoplasms (MCNs) (0/10), neuroendocrine neoplasms (0/52), acinar cell neoplasms (0/16), serous cystadenomas (0/10), and solid-pseudopapillary neoplasms (0/14). We found GNAS mutations in 55/91 IPMNs with or without associated invasive carcinoma, solely in intestinal-type (78 %, 21/27) and gastric-type (62 %, 34/55) IPMNs. Of the IPMN-associated adenocarcinomas, mucinous-subtype tumours harboured GNAS mutations more frequently (83 %, 5/6) than tubular-subtype tumours (25 %, 6/24) (p = 0.02). We separately analysed GNAS in the adenocarcinoma and the IPMN component in the IPMN-associated adenocarcinomas. In all mucinous-subtype tumours, the two components exhibited identical genotypes. In contrast, the two components in 8 of 24 tubular-subtype tumours exhibited different genotypes, indicating intratumour heterogeneity. In conclusion, mucinous carcinomas with or without associated IPMN as well as IPMNs frequently harbour a GNAS mutation, reinforcing the notion that these constitute a spectrum of pancreatic tumours. Clinically and pathologically, these tumours are associated, but GNAS mutation sheds further light on this spectrum.

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Acknowledgments

The authors thank Chieko Yamada, Noriko Shibata, Ayako Nonaka, and Motoko Nimura for their excellent technical assistance with the molecular genetics. This work was supported in part by a Grant-in-Aid (B-25293090) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology and Molecular Diagnostics, Aichi Cancer Centre Hospital, Kanokoden 1-1, Chikusa-ku, Nagoya, 464-8681, Japan

    Waki Hosoda, Eiichi Sasaki, Yoshiko Murakami & Yasushi Yatabe

  2. Department of Gastroenterology, Aichi Cancer Centre Hospital, Kanokoden 1-1, Chikusa-ku, Nagoya, 464-8681, Japan

    Kenji Yamao

  3. Department of Gastrointestinal Surgery, Aichi Cancer Centre Hospital, Kanokoden 1-1, Chikusa-ku, Nagoya, 464-8681, Japan

    Yasuhiro Shimizu

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  1. Waki Hosoda
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Correspondence to Yasushi Yatabe.

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Hosoda, W., Sasaki, E., Murakami, Y. et al. GNAS mutation is a frequent event in pancreatic intraductal papillary mucinous neoplasms and associated adenocarcinomas. Virchows Arch 466, 665–674 (2015). https://doi.org/10.1007/s00428-015-1751-6

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