scholarly journals Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus

2018 ◽  
Vol 24 (8) ◽  
pp. 1881-1890 ◽  
Author(s):  
Alexa B. Schrock ◽  
Dean Pavlick ◽  
Samuel J. Klempner ◽  
Jon H. Chung ◽  
Brady Forcier ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Hybrid Capture ◽  
Tumor Dna

Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with advanced cancers of the GI tract and anus.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 618-618 ◽  
Author(s):  
Alexa Betzig Schrock ◽  
Lauren Young ◽  
Samuel Jacob Klempner ◽  
Rodolfo Bordoni ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Molecular Profiling ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Tissue Sampling ◽  
Gi Tract ◽  
Hybrid Capture ◽  
Non Invasive ◽  
Clinical Support ◽  
Average Maximum ◽  
Tumor Dna

618 Background: The treatment of GI carcinomas (CA) is influenced by the presence or absence of prognostic and predictive genomic alterations (GA). Tissue sampling is the historical platform for genomic biomarker assessment, but non-invasive ctDNA assay provides an alternative when tissue is unavailable or cannot be safely obtained. Methods: Hybrid-capture based genomic profiling using a ctDNA assay (FoundationACT) was performed on blood samples from 82 consecutive pts with lower alimentary canal CA. Results: Median age was 62 (range 28-92) and 61% were male. Anatomic breakdown included CRC (n = 51), esophageal (n = 9), gastric (n = 8), gastroesophageal (n = 3) and small bowel adenoCA (SBA, n = 2), anus squamous cell CA (n = 5), and other GI CA (n = 4). At least one GA was reported in 72% of cases. In 23 cases with no GA reported, the average maximum somatic allele frequency was 0.17% (95% CI: 0-0.6%) vs. 16.7% (95% CI: 0-54.4%) for the 59 cases with GAs (P < 0.0001). For the 3 of 18 patients with both blood and tissue testing performed and samples collected within a 30-day interval, 8/9 (89%) GA detected in tissue were also detected in ctDNA. An average of 1.7 GA/sample were detected in ctDNA. The most commonly altered genes were TP53 (61%), KRAS (24%), BRAF (10%) and PIK3CA (10%). Comparative analysis using the tissue-based Foundation Core database showed a similar trend with overall slightly higher frequencies of GAs in individual genes . RAF and RAS short variants (SV) were exclusive to lower GI and anal CA. KRAS and RAF1 amplification (amp) occurred only in esophageal CA (4/11, 36%). FGFR SV or amp was identified in 3 cases across the cohort. Of CRC, 4 (8%) had ≥ 1 ERBB2 activating SV or amp, 2 (4%) had IDH1/2 hotspot SV, and 2 (4%) had BRCA2 inactivating alterations. ERBB2 activating SV and EGFR amp were found in a SBA and an esophagus CA, respectively. A kinase fusion was identified as the sole driver in 1 CRC ( STRN-ALK) and 1 SBA ( GOPC-ROS1). Outcomes to targeted therapies will be presented for the available subset of patients. Conclusions: Our results provide early clinical support and confirm that hybrid-capture based ctDNA testing can reliably detect all 4 classes of GA and provide a molecular profiling option for patients with GI CA.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with advanced hepatocellular carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15606-e15606
Author(s):  
Mao Li ◽  
Ailin Wei ◽  
Wenzhuan Xie ◽  
Jing Zhao ◽  
Zhengyi Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circulating Tumor Dna ◽  
Chinese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Genomic Profiling ◽  
Promising Alternative ◽  
Hybrid Capture ◽  
Advanced Hcc ◽  
Tissue Biopsy ◽  
Tumor Dna

e15606 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with a particularly high prevalence in China. The genomic profiling in HCC had been widely explored with tissue biopsy, however, given the intrinsic risks of invasive approach, blood-based circulating tumor DNA (ctDNA) has been proposed as a promising alternative. In this study, we aim to investigate whether the ctDNA may serve as a reliable tool to provide a more accurate molecular snapshot of HCC in Chinese patients. Methods: Plasma samples from 385 Chinese patients with advanced HCC were assayed for somatic genomic alternations by hybrid capture-based next-generation sequencing (NGS) with 150 genes and a mean sequencing depth of more than 3000×. The results were compared with our internal tissue genomic database of Chinese HCC patients (N = 873) tested by NGS and TCGA database (N = 373) tested by whole exome sequencing. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations, gene rearrangement and fusions were assessed. Results: Among 385 patients with ctDNA testing, somatic genomic alternations were detected in 97% of the patients (median = 5 alterations/patient). The most prevalent SNV mutations from ctDNA sequencing were TP53 (45.7%), TERT (19.5%), CTNNB1 (12.5%), and LRP1B (8.3%) compared to our tissue database (TP53 (61.2%), CTNNB1 (15.6%), TERT (13.3%), and LRP1B (11.0%)). While in TCGA database, the most common SNV mutations were found in TP53 (30.1%), CTNNB1 (26.0%), LRP1B (8.8%), ARID1A (8.6%), and SPTA1 (7.5%). Moreover, the level of MSAF was associated with detectable variant types, evidenced by a significant higher MSAF level observed when amplifications (P < 0.0001) or fusions (P = 0.008) were detected in the samples. Conclusions: Molecular analysis of patients with advanced HCC through ctDNA can serve as a reliable alternative to tissue biopsy. Chinese HCC patients may have different mutational landscapes to Western population. The utility of ctDNA analysis can provide therapeutically exploitable genomic profiles to identify potentially actionable gene alterations for targeted therapies.

scholarly journals Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Advanced Ovarian Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Wenbin Shen ◽  
Boer Shan ◽  
Shanhui Liang ◽  
Junling Zhang ◽  
Yangyang Yu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mutation Frequency ◽  
Advanced Ovarian Cancer ◽  
Circulating Tumor Dna ◽  
Cancer Tissue ◽  
Genomic Profiling ◽  
Tissue Samples ◽  
Hybrid Capture ◽  
Ovarian Cancer Tissue ◽  
Tumor Dna

Objective: We conducted this study to characterize somatic genomic alterations in circulating tumor DNA (ctDNA) from patients with ovarian cancer and compare GAs detected in ctDNA with tissue databases.Methods: Hybrid capture-next generation sequencing genomic profiling of 150 genes was performed on ctDNA from 138 patients with ovarian cancer with 1,500× sequencing depth. The GAs detected in ctDNA were compared with those in our ovarian cancer tissue database (N = 488) and the Cancer Genome Atlas (TCGA) database (N = 489).Results: 115 patients (83%) had at least 1 GA detected in ctDNA. The most frequently altered genes detected in ctDNA were TP53 (72%), KRAS (11%), LRP1B (10%), ZNF703 (9%) and NF1 (8%). Comparative analysis with our tissue database showed similar frequencies of GAs per gene, although PIK3CA and KRAS mutations were more frequent in tissue and ctDNA, respectively (p &lt; 0.05). Gene amplification and rearrangement were more frequent in ctDNA samples. The mutation frequency of homologous recombination repair associated-genes, VEGF signal/angiogenesis pathways, RAS pathways, NOTCH pathways and MSI-H ratio was not statistically different either in ctDNA or in tissue database. However, the mutation frequency of AKT, PIK3CA, PTEN and STK11 in PI3K/AKT/mTOR pathway was significantly lower than that in tissue samples (p &lt; 0.05).Conclusions: Our results suggest that genomic profiling of ctDNA could detect somatic GAs in a significant subset of patients with ovarian cancer. Hybrid capture-NGS based on liquid biopsy has the potential capability to serve as a substitute to tissue biopsy and further studies are warranted.

scholarly journals Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Non–Small Cell Lung Cancer

2019 ◽  
Vol 14 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Alexa B. Schrock ◽  
Allison Welsh ◽  
Jon H. Chung ◽  
Dean Pavlick ◽  
Eric H. Bernicker ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Hybrid Capture ◽  
Tumor Dna

scholarly journals Genomic profiling of cell-free circulating tumor DNA in patients with colorectal cancer and its fidelity to the genomics of the tumor biopsy

2019 ◽  
Vol 10 (5) ◽  
pp. 831-840 ◽  
Author(s):  
Gerald Li ◽  
Dean Pavlick ◽  
Jon H. Chung ◽  
Todd Bauer ◽  
Bradford A. Tan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Tumor Biopsy ◽  
Tumor Dna

scholarly journals P2.03b-023 Circulating Tumor DNA (ctDNA)-Based Genomic Profiling of Known Cancer Genes in Lung Squamous Cell Carcinoma (LUSC)

2017 ◽  
Vol 12 (1) ◽  
pp. S947-S948
Author(s):  
Vincent Lam ◽  
Hai Tran ◽  
Kimberly Banks ◽  
Waree Rinsurongkawong ◽  
Vassiliki Papadimitrakopoulou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Cancer Genes ◽  
Tumor Dna

Circulating tumor DNA-based genomic profiling of small bowel adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3523-3523
Author(s):  
Pat Gulhati ◽  
Karan Pandya ◽  
Hiba I. Dada ◽  
Christopher R. Cogle ◽  
Jason S. Starr ◽  
...  
Keyword(s):  
Small Bowel ◽  
Large Scale ◽  
Clinical Decision Making ◽  
Circulating Tumor Dna ◽  
Therapeutic Resistance ◽  
Molecular Entity ◽  
Small Bowel Adenocarcinoma ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling ◽  
Tumor Dna

3523 Background: Small bowel adenocarcinoma (SBA) is a rare malignancy, with lower incidence, later stage at diagnosis, and worse overall survival compared to other intestinal cancers, such as colorectal cancer (CRC). Since the majority of small bowel tumors are not accessible to endoscopic biopsy, comprehensive genomic profiling using circulating tumor DNA (ctDNA) may enable non-invasive detection of targetable genomic alterations (GA) in SBA patients. In this study, we characterize the ctDNA GA landscape in SBA. Methods: Analysis of 299 ctDNA samples prospectively collected from 265 SBA patients between 2017 to 2020 was performed using a 73 gene next generation sequencing panel (Guardant360). A subset of patients underwent longitudinal analysis of changes in GA associated with systemic therapy. Results: Of the 265 patients, 160 (60.3%) were male; the median age was 66 (range: 21-93 years). The most common GA identified in SBA patients included TP53 [58%], KRAS [44%], and APC [40%]. MSI was detected in 3.4% of SBA patients. When stratified by primary tumor location, APC, KRAS, TP53, PIK3CA, and ARID1A were the most common GA identified in both duodenal and jejunal adenocarcinomas. ERBB2, BRCA2 and CDK6 alterations were enriched in duodenal adenocarcinoma, while NOTCH and BRAF alterations were enriched in jejunal adenocarcinoma. The most common currently-targetable GA identified were ATM [18%], PIK3CA [17%], EGFR [15%], CDK4/6 [11%], BRAF [10%], and ERBB2 [10%]. Unique differences in GA between SBA and CRC were identified: i) the majority of ERBB2 alterations are mutations (89%) in the extracellular domain and kinase domain, not amplifications (11%); ii) the majority of BRAF alterations are non V600E mutations (69%) and amplifications (28%); iii) there is a significantly lower rate of APC mutations (40%). Alterations in DNA damage response pathway proteins, including ATM and BRCA 1/2, were identified in 30% of SBA patients. ATM alterations were more common in patients ³65 years old. The most common mutations predicted to be related to clonal hematopoiesis of indeterminate potential were TP53, KRAS and GNAS. Longitudinal ctDNA analysis in 4 SBA patients revealed loss of mutations associated with therapeutic response (TP53 R342*, MAPK3 R189Q) and acquired mutations associated with therapeutic resistance (NF1 R1968*, MET S170N, RAF1 L613V). Conclusions: This study represents the first large-scale blood-based ctDNA genomic profiling of SBA. SBA represents a unique molecular entity with differences in frequency and types of GA compared to CRC. Variations in GA were noted based on anatomic origin within the small intestine. Longitudinal ctDNA monitoring revealed novel GA associated with therapeutic resistance. Identification of multiple targetable GA may facilitate clinical decision making and improve patient outcomes in SBA, especially when a tissue biopsy is not feasible or sufficient for comprehensive genomic profiling.

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