Data from: Reporting tumor molecular heterogeneity in histopathological diagnosis
Data files
Jul 17, 2015 version files 9.99 GB
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AVC1.bam
54.95 MB
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AVC2.bam
44.24 MB
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AVC3.bam
82.21 MB
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AVC4.bam
97.11 MB
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AVC5.bam
204.77 MB
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ffpe_dilutioncurve_0_percent_hepatocarcinoma.bam
422.36 MB
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ffpe_dilutioncurve_10_percent_hepatocarcinoma.bam
170.40 MB
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ffpe_dilutioncurve_100_percent_hepatocarcinoma.bam
385.94 MB
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ffpe_dilutioncurve_25_percent_hepatocarcinoma.bam
165.69 MB
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ffpe_dilutioncurve_50_percent_hepatocarcinoma.bam
206.05 MB
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ffpe_dilutioncurve_75_percent_hepatocarcinoma.bam
304.38 MB
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ffpe_dilutioncurve_90_percent_hepatocarcinoma.bam
187.39 MB
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ffpe_dilutioncurve_95_percent_hepatocarcinoma.bam
88.29 MB
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frozen_dilutioncurve_0_percent_tumor.bam
288.10 MB
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frozen_dilutioncurve_1_percent_tumor.bam
331.90 MB
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frozen_dilutioncurve_10_percent_tumor.bam
343.02 MB
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frozen_dilutioncurve_15_percent_tumor.bam
299.24 MB
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frozen_dilutioncurve_2.5_percent_tumor.bam
336.15 MB
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frozen_dilutioncurve_20_percent_tumor.bam
304.16 MB
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frozen_dilutioncurve_25_percent_tumor.bam
277.54 MB
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frozen_dilutioncurve_5_percent_tumor.bam
338.29 MB
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frozen_dilutioncurve_50_percent_tumor.bam
355.74 MB
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frozen_dilutioncurve_7.5_percent_tumor.bam
364.09 MB
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GC1.bam
108.26 MB
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GC2.bam
149.97 MB
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GC3.bam
94.13 MB
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GC4.bam
95.97 MB
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GC5.bam
128.98 MB
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HCC1.bam
178.74 MB
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HCC2.bam
198.45 MB
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HCC3.bam
141.83 MB
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HCC4.bam
277.16 MB
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HCC5.bam
124.66 MB
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ICC1.bam
122.70 MB
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ICC2.bam
69.38 MB
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ICC3.bam
91.75 MB
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ICC4.bam
55.63 MB
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ICC5.bam
214.22 MB
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IPMN1.bam
108.34 MB
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IPMN2.bam
202.90 MB
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IPMN3.bam
179.91 MB
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IPMN4.bam
149.45 MB
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IPMN5.bam
154.61 MB
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PDAC1.bam
112.04 MB
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PDAC2.bam
118.88 MB
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PDAC3.bam
98.92 MB
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PDAC4.bam
121.24 MB
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PDAC5.bam
122.70 MB
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SPT1_FFPE.bam
48.53 MB
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SPT1_FROZEN.bam
81.60 MB
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SPT2_FFPE.bam
130.52 MB
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SPT2_FROZEN.bam
101.48 MB
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SPT3_FFPE.bam
71.78 MB
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SPT3_FROZEN.bam
137.27 MB
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SPT4_FFPE.bam
69 MB
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SPT4_FROZEN.bam
87.86 MB
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SPT5_FFPE.bam
86.51 MB
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SPT5_FROZEN.bam
107.25 MB
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.