12IN - Mutational and chromosomal surveys of pancreatic tumors

Date 30 September 2012
Event ESMO Congress 2012
Session The impact of the cancer genome project and high-throughput analyses on personalised oncology: Today and tomorrow
Topics Pancreatic Cancer
Personalised/Precision medicine
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Aldo Scarpa
Authors A. Scarpa
  • Patologia E Diagnostica, Anatomia Patologica, University of Verona, 37134 - Verona/IT


Mirroring the cellular diversity within the pancreas, the spectrum of distinct pancreatic neoplasms shows histological and molecular features partially recalling the characteristics of the cell of origin. Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplasm and bears the worst prognosis. Pancreatic neuroendocrine tumors (pNETs) are the second most common neoplasm with an incidence that is considerably increasing over the last 30-years. Our limited knowledge of the genetic basis of these diseases based on candidate gene approaches has now been expanded by the use of massive parallel sequencing (MPS). These have helped to uncover the genomic landscape of cancers showing that, beyond high frequency mutations (Table 1), a plethora of different molecular features are identified at low frequency and define potential cancer subgroups of clinical interest. This is particularly true for PDAC that represents the real “social problem” among pancreatic neoplasms. Recent works exploring the structural variations' landscape of PDAC have also highlighted a high degree of genetic heterogeneity in metastatic deposits, which substantially reflects the presence of different subclones within the primitive disease. When ignored, molecular heterogeneity can lead to failure in therapeutic treatments, as drugs that may have efficacy in subgroups of patients with specific molecular phenotypes may show marginal response when tested in a large group of unselected patients. This calls for the revisitation of the classical pathological diagnosis of cancer where the description of intra-tumor heterogeneity at both morphological and molecular level are taken into account for a diagnoistic report to be clinically useful to devise first, second and additional therapeutic choices. Table: 12IN

Commonly mutated genes in different pancreatic neoplasms.

Tumor Typea Genesb
PDAC KRAS (100%), TP53 (85%), SMAD4 (38%), CDKN2A (25%)
pNET MEN1 (44%), DAXX (25%), ATRX (17%), PTEN (7%), TSC2 (9%)
IPMN KRAS (62%), GNAS (62%), RNF43 (75%)
MCN KRAS (75%), RNF43 (37%)
SPN CTNNB1 (100%)

§ PDAC, pancreatic ductal adenocarcinoma; pNET, pancreatic neuroendocrine tumors; IPMN, intraductal papillary mucinous neoplasm; MCN, mucinous cystic neoplasm; SPN, solid pseudopapillary neoplasm.

b Percentages within brackets refer to mutation frequencies assessed in specific clinical cohorts


The author has declared no conflicts of interest.