Dataset Information

Reporting tumor molecular heterogeneity in histopathological diagnosis.

ABSTRACT:

Background

Detection of molecular tumor heterogeneity has become of paramount importance with the advent of targeted therapies. Analysis for detection should be comprehensive, timely and based on routinely available tumor samples.

Aim

To evaluate the diagnostic potential of targeted multigene next-generation sequencing (TM-NGS) in characterizing gastrointestinal cancer molecular heterogeneity.

Methods

35 gastrointestinal tract tumors, five of each intestinal type gastric carcinomas, pancreatic ductal adenocarcinomas, pancreatic intraductal papillary mucinous neoplasms, ampulla of Vater carcinomas, hepatocellular carcinomas, cholangiocarcinomas, pancreatic solid pseudopapillary tumors were assessed for mutations in 46 cancer-associated genes, using Ion Torrent semiconductor-based TM-NGS. One ampulla of Vater carcinoma cell line and one hepatic carcinosarcoma served to assess assay sensitivity. TP53, PIK3CA, KRAS, and BRAF mutations were validated by conventional Sanger sequencing.

Results

TM-NGS yielded overlapping results on matched fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues, with a mutation detection limit of 1% for fresh-frozen high molecular weight DNA and 2% for FFPE partially degraded DNA. At least one somatic mutation was observed in all tumors tested; multiple alterations were detected in 20/35 (57%) tumors. Seven cancers displayed significant differences in allelic frequencies for distinct mutations, indicating the presence of intratumor molecular heterogeneity; this was confirmed on selected samples by immunohistochemistry of p53 and Smad4, showing concordance with mutational analysis.

Conclusions

TM-NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, moving one step closer to a next-generation histopathologic diagnosis that integrates morphologic, immunophenotypic, and multigene mutational analysis on routinely processed tissues, essential for personalized cancer therapy.

SUBMITTER: Mafficini A

PROVIDER: S-EPMC4134249 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Reporting tumor molecular heterogeneity in histopathological diagnosis.

Mafficini Andrea A Amato Eliana E Fassan Matteo M Simbolo Michele M Antonello Davide D Vicentini Caterina C Scardoni Maria M Bersani Samantha S Gottardi Marisa M Rusev Borislav B Malpeli Giorgio G Corbo Vincenzo V Barbi Stefano S Sikora Katarzyna O KO Lawlor Rita T RT Tortora Giampaolo G Scarpa Aldo A

PloS one 20140815 8

<h4>Background</h4>Detection of molecular tumor heterogeneity has become of paramount importance with the advent of targeted therapies. Analysis for detection should be comprehensive, timely and based on routinely available tumor samples.<h4>Aim</h4>To evaluate the diagnostic potential of targeted multigene next-generation sequencing (TM-NGS) in characterizing gastrointestinal cancer molecular heterogeneity.<h4>Methods</h4>35 gastrointestinal tract tumors, five of each intestinal type gastric ca ...[more]

PMID: 25127237

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Dataset Information

Reporting tumor molecular heterogeneity in histopathological diagnosis.

Background

Aim

Methods

Results

Conclusions

Publications

Reporting tumor molecular heterogeneity in histopathological diagnosis.

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