Chromosomal microarray provides enhanced targetable gene aberration detection when paired with next generation sequencing panel in profiling lung and colorectal tumors

Mukherjee, Sandeep; Ma, Zeq; Wheeler, Scott R.; Sathanoori, Malini; Coldren, Christopher D.; Prescott, James L.; Kozyr, Natalia; Bouzyk, Mark; Correll, Mick; Ho, Hao; Chandra, Pranil; Lennon, Patrick A.

doi:10.1016/j.cancergen.2015.12.011

Cited by 7 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hypermutated tumors are characterized by elevated levels of MSI and defects in DNA MMR mechanisms. An activating mutation of BRAF is frequently presented in the hypermutated tumor [119,120]. Recurrent mutation of TP53 , KRAS , APC , and PIK3CA has been consistently reported in previous studies and it is notable that the significantly frequent KRAS mutation is identified in non-hypermutated tumors (Table 3) [114,119,121].…”

Section: Next-generation Sequencing Cancer Panelmentioning

confidence: 96%

Molecular Testing for Gastrointestinal Cancer

Lee

Kim

Kwak

et al. 2017

J Pathol Transl Med

View full text Add to dashboard Cite

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

show abstract

Section: Next-generation Sequencing Cancer Panelmentioning

confidence: 96%

Molecular Testing for Gastrointestinal Cancer

Lee

Kim

Kwak

et al. 2017

J Pathol Transl Med

View full text Add to dashboard Cite

show abstract

“…These methodologies are complementary to each other and are essential for genetic discovery projects. Further, targeted sequencing of multiple specific genomic regions may offer an easier and less expensive alternative strategy in routine molecular diagnostics of cancer allowing a more detailed cancer genetic lesions to be obtained [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Targeted next generation sequencing identifies somatic mutations and gene fusions in papillary thyroid carcinoma

Zhang

Feng

et al. 2017

Oncotarget

View full text Add to dashboard Cite

138 papillary thyroid carcinoma (PTC) samples were assessed for somatic mutation profile and fusion genes by targeted resequencing using a cancer panel (ThyGenCapTM) targeting 244 cancer-related genes and 20 potential fusion genes. At least one genetic alteration (including mutations and fusion genes) was observed in 118/138 (85.5%) samples. The most frequently mutated gene was BRAF V600E (57.2%). Moreover, we identified 11 fusion genes including eight previously reported ones and three novel fusion genes, UEVLD-RET, OSBPL9-BRAF, and SQSTM1-NTRK3. Alterations affecting the mitogen-activated protein kinase (MAPK) signaling pathway components were seen in 69.6% of the PTC cases and all of these driver mutations were mutually exclusive. Univariate analysis ascertained that the fusion genes were strongly associated with distinct clinicopathological characteristics, such as young age, local invasion, extensive metastasis, and disease stage. In conclusion, our approach facilitated simultaneous high-throughput detection of gene fusions and somatic mutations in PTC samples.

show abstract

“…To date NGS technologies have had significant limitations with respect to CNV detection compared to microarray technologies [8,23,24]. Advances in NGS chemistries and analytics tools could make NGS and microarray technologies very complementary and increase the number of variants detected in human cancers [22,24].…”

Section: Future Directionsmentioning

confidence: 99%

Utilization of the oncoscan microarray assay in cancer diagnostics

2017

View full text Add to dashboard Cite

Current strategies for cancer patient management include the use of genomic and proteomic test results to help guide therapeutic selection. The need for multi-target variant analysis is highlighted by the growing number of novel therapies to treat tumors with specific profiles and the increasing recognition that cancer is an extremely heterogeneous syndrome. Microarray analysis is a powerful genomic tool that provides genome-wide genetic information that is critical for guiding cancer treatments. Unlike constitutional applications of microarray analysis which are performed on whole blood samples, microarray analysis of solid tumors is challenging because tumor tissues are typically formalin fixed and paraffin embedded (FFPE). Genomic DNA extracted from FFPE tissues can also be fragmented into small pieces and yield much lower concentrations of DNA. We validated and implemented the Affymetrix OncoScan® FFPE assay to enable genome-wide analysis from these types of samples. The Affymetrix OncoScan® assay utilizes molecular inversion probes that generate multiplexed array hybridization targets from as short as 40 base-pairs of sequence and as low as approximately 80 ng of genomic DNA. OncoScan microarray analysis provides genomic information that includes structural variations, copy number variations and SNPs in a timely and a cost-effective manner from FFPE tumor tissues.

show abstract

Chromosomal microarray provides enhanced targetable gene aberration detection when paired with next generation sequencing panel in profiling lung and colorectal tumors

Cited by 7 publications

References 44 publications

Molecular Testing for Gastrointestinal Cancer

Molecular Testing for Gastrointestinal Cancer

Targeted next generation sequencing identifies somatic mutations and gene fusions in papillary thyroid carcinoma

Utilization of the oncoscan microarray assay in cancer diagnostics

Contact Info

Product

Resources

About