Genomic somatic alterations of human epidermal growth factor-2 (HER2) gene: A pan-cancer analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3112-3112
Author(s):  
Xinhua Zhu ◽  
Yong Zhou ◽  
Yuzi Zhang ◽  
Shangli Cai
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Circulating Tumor Dna ◽  
Her2 Amplification ◽  
Her2 Gene ◽  
Tract Cancer ◽  
Epidermal Growth ◽  
Tumor Types

3112 Background: Human epidermal growth receptor 2 (HER2) is a well-known oncogenic drive gene with multiple targeted therapeutic options. In this study, we aim to assess the landscape of HER2 alterations in solid tumors and evaluate the feasibility of circulating tumor DNA (ctDNA) tested by next-generation sequence (NGS) as a tool to detect HER2 alterations. Methods: Alterations of HER2 by NGS (Illumina NextSeq 500) were queried in 3D Medicines database. The mean depth of tissue and circulating tumor DNA (ctDNA) test was 500X and 5000X, respectively. 11,013 patients tested using tumor tissue and 6,970 patients tested using ctDNA were included in this analysis. Results: Of 11,013 patients tested using tumor tissue, any HER2 and known or likely deleterious HER2 mutations were identified in 739 (6.7%) and 531 (4.8%) patients, respectively. Of 531 patients who carried known or likely deleterious HER2 mutations, 263 (49.5%) had HER2 amplification and 259 (48.8%) had single nucleotide variations (SNVs). Across all tumor types, breast cancer was found to have the highest frequency of HER2 amplification (14.9%, 48/323), followed by gastric cancer (6.6%, 31/470) and biliary tract cancer (5.8%, 33/571). Moreover, 11% (8/73) of duodenal cancer, 4.5% (7/154) of urothelial cancer, 3.8% (18/470) of gastric cancer, 3.1% (142/4555) of lung cancer, 2.9% (17/571) of biliary tract cancer, 2.8% (44/1562) of colorectal cancer and 2.7% (9/323) of breast cancer carried known or likely deleterious HER2 SNVs. Of 6970 patients tested using ctDNA, any HER2 and known or likely deleterious HER2 mutations were identified in 592 (8.5%) and 277 (4.0%) patients, respectively. In the ctDNA cohort, 15.7% (36/230) of breast cancer and 3.1% (5/161) of biliary tract cancer carried HER2 amplification. However, 11.6% (20/173) of gastric cancer had HER2 amplification tested by ctDNA which was higher than that tested using tissue. Furthermore, 5.6% (13/230) of breast cancer, 4.5% (2/44) of urothelial cancer, 3.4% (6/173), 2.5% of biliary tract cancer and 2.0% (94/4586) lung cancer harbored known or likely deleterious HER2 SNVs in ctDNA cohort. Conclusions: HER2 alterations existed across tumor types and the landscape of genomic alterations in HER2 gene varied according to different type of tumor. In addition, ctDNA can be used as a potential tool to detect HER2 alterations.

ASSOCIATION BETWEEN BILIARY TRACT CANCER AND GASTRIC CANCER

The Lancet ◽  
1983 ◽  
Vol 322 (8360) ◽  
pp. 1204-1205 ◽  
Author(s):  
C. Caygill ◽  
R. Hall ◽  
M.J. Hill
Keyword(s):  
Gastric Cancer ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Tract Cancer

Genotyping of circulating tumor DNA in biliary tract cancer to reveal diagnostic and prognostic information.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 291-291 ◽  
Author(s):  
Andreas Wolfgang Berger ◽  
Thomas Jens Ettrich ◽  
Daniel Schwerdel ◽  
Anna Dolnik ◽  
Florian Beuter ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Palliative Treatment ◽  
Tumor Tissue ◽  
Locally Advanced ◽  
Circulating Tumor Dna ◽  
Imaging Data ◽  
Tract Cancer ◽  
Pretreated Patients ◽  
Tumor Dna

291 Background: Biliary tract cancer (BTC) shows increasing incidence and is associated with a high mortality. Diagnosis is difficult due to the frequently occurring inaccessibility of the tumor for biopsy. Noninvasive approaches for (i) assessing and (ii) monitoring the tumor-specific molecular setup are desirable. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal. Methods: Blood and tumor tissue samples from patients with locally advanced or metastatic BTC prior to and during palliative treatment were collected. Tumor tissue and corresponding ctDNA samples underwent targeted genotyping of the 15 most frequently mutated genes in BTC. Findings were correlated with clinical and imaging data. Results: 24 therapy naive patients with histologically confirmed BTC were included for analyses. The overall mutational concordance (blood/tissue) was 74% and 92% for intrahepatic tumors. The mean variant allele frequency (VAF) in tumor tissue of therapy naïve patients was significantly higher compared to the respective ctDNA (p = 0.0291). In turn, the sequencing depth for ctDNA was significantly deeper (p = 0.0001), enabling us to detect also rare variants. Mean ctDNA VAF at baseline significantly correlated with tumor load (Spearman, r = 0.4073, p = 0.0433) and, exclusively for intrahepatic tumors, also with progression-free survival (Spearman, r = -0.5878, p = 0.0386). During 1st line palliative treatment, we detected a change in the mutational landscape in 36% of cases, Moreover, we had access to ctDNA samples of 5 pretreated patients. While ctDNA samples of therapy naïve patients (n = 23) showed a mean of 0.78 mutations per patient, ctDNA samples of pretreated patients (n = 5) exhibited a mean of 0.4 mutations (p = 0.5519). Conclusions: The molecular landscape of BTC is depicted in ctDNA which may enable to adapt diagnostic and therapeutic strategies to the specific molecular setup present at a certain time. In contrast, the use of targeted resequencing is likely to be insufficient for a comprehensive assessment of treatment induced BTC evolution. For this purpose, we suggest a more extensive analysis of ctDNA by broader sequencing applications and the incorporation of epigenetics.

Genotyping of circulating tumor DNA in biliary tract cancer reveals diagnostic and prognostic information.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e16147-e16147 ◽  
Author(s):  
Andreas Wolfgang Berger ◽  
Thomas Jens Ettrich ◽  
Daniel Schwerdel ◽  
Anna Dolnik ◽  
Florian Beuter ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Circulating Tumor Dna ◽  
Prognostic Information ◽  
Tract Cancer ◽  
Tumor Dna

Blood-based genomic profiling of circulating tumor DNA from patients with advanced biliary tract cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1576-1576
Author(s):  
Junying Wang ◽  
Jia Song ◽  
Jing Zhao ◽  
Yuzi Zhang ◽  
Shangli Cai ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Tumor Heterogeneity ◽  
Circulating Tumor Dna ◽  
Pi3k Pathway ◽  
Chinese Patients ◽  
Tissue Samples ◽  
Tract Cancer ◽  
Tumor Dna

1576 Background: Biliary tract cancer (BTC) is a highly lethal malignancy as diagnosis occurring at late stages and marginally sensitive to chemotherapy. Increasing evidence indicates targeted therapeutics may provide new hope for improving clinical response in BTC, hence better comprehending the genomic profile is particularly important. However, tissue of BTC is highly wide tumor heterogeneity and often inadequate for molecular characterization, a proper method is urgently needed. Circulating tumor DNA (ctDNA) is an emerging technology for detecting actionable alterations, and may be regarded as a reliable tool to reveal genomic signature. Methods: Next-generation sequencing (NGS) targeted 150 cancer-related genes was used to detect blood-based ctDNA from 154 Chinese patients with BTC. The mean sequencing depth was more than 3000×. Somatic genomic alternations (GA) including single nucleotide variation (SNV), copy number variation (CNV) and fusion were analyzed and compared with an internal tissue genomic database (545 Chinese patients with BTC) tested by NGS and TCGA database (n = 227) tested by the whole exome sequencing (WES). Allele frequency (AF) represented the percentage of mutant allele reads relative to total allele reads (mutant plus wild type). Maximum somatic allele frequency (MSAF) was defined as the maximum AF (0.1% < AF < 35%) of all the somatic alterations identified per sample. Results: Among ctDNA database, at least one GA was found in 95% (147/154) of samples (a median of 4 GA per patient). The median MSAF across all cases was 6.47% (range, 0%-34.8%). Pathologic type (P < 0.001) and sex (P < 0.001) were significantly related with MSAF, respectively. Frequencies of SNV in commonly mutated genes from ctDNA were similar to those observed among tissue samples, like TP53 (35.1% vs 40.4%) and KRAS (20.1% vs 22.6%), however, a little lower in TCGA database (TP53 24.2%; KRAS 10.1%). Besides, the consistency of CNV detected from ctDNA and tissue was relatively poor, and tumor heterogeneity might be in charge of this phenomenon. Among the highly frequent mutations (AF > 5%) in ctDNA, 45% of genes was considered as druggable targets, such as EGFR/RAS/RAF pathway and AKT/mTOR/PI3K pathway. Conclusions: These findings demonstrated that ctDNA tested by NGS was feasible in revealing genomic profiles and identifying potential therapeutic targets. Noninvasive ctDNA could be used as a complementary approach to tissue testing in patients with metastatic BTC.

scholarly journals Epidermal growth factor receptor (EGFR) in Biliary tract cancer

HPB ◽  
2016 ◽  
Vol 18 ◽  
pp. e466
Author(s):  
R.V. Gomes ◽  
P.T. Vidigal ◽  
K.A. Damasceno ◽  
M. Rodrigues ◽  
V. Resende
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Growth Factor Receptor ◽  
Tract Cancer ◽  
Epidermal Growth

scholarly journals Genomic Profiling of Blood-Derived Circulating Tumor DNA from Patients with Advanced Biliary Tract Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Chen Chen ◽  
Tao Wang ◽  
Mengmei Yang ◽  
Jia Song ◽  
Mengli Huang ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Circulating Tumor Dna ◽  
Chinese Patients ◽  
Ras Signaling ◽  
Genomic Alterations ◽  
Tissue Samples ◽  
Genomic Changes ◽  
Tract Cancer ◽  
Tumor Dna

Background: Biliary tract cancer is a highly lethal malignancy with poor clinical outcome. Accumulating evidence indicates targeted therapeutics may provide new hope for improving treatment response in BTC, hence better understanding the genomic profile is particularly important. Since tumor tissue may not be available for some patients, a complementary method is urgently needed. Circulating tumor DNA (ctDNA) provides a noninvasive means for detecting genomic alterations, and has been regarded as a promising tool to guide clinical therapies.Methods: Next-generation sequencing of 150 cancer-related genes was used to detect gene alterations in blood-derived ctDNA from 154 Chinese patients with BTC. Genomic alterations were analyzed and compared with an internal tissue genomic database and TCGA database.Results: 94.8% patients had at least one change detected in their ctDNA. The median maximum somatic allele frequency was 6.47% (ranging 0.1–34.8%). TP53 and KRAS were the most often mutated genes. The frequencies of single nucleotide variation in commonly mutated genes in ctDNA were similar to those detected in tissue samples, TP53 (35.1 vs. 40.4%) and KRAS (20.1 vs. 22.6%). Pathway analysis revealed that mutated genes were mapped to several key pathways including PI3K-Akt, p53, ErbB and Ras signaling pathway. In addition, patients harboring LRP1B, TP53, and ErbB family mutations presented significantly higher tumor mutation burden.Conclusions: These findings demonstrated that ctDNA testing by NGS was feasible in revealing genomic changes and could be a viable alternative to tissue biopsy in patients with metastatic BTC.

Sign in / Sign up

Export Citation Format

Share Document