Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe–Based Single-Nucleotide Polymorphism Array

Singh, Rajesh R.; Mehrotra, Meenakshi; Chen, Hui; Almohammedsalim, Alaa A.; Sahin, Ayesagul; Bosamra, Alex; Patel, Keyur P.; Routbort, Mark J.; Lu, Xinyan; Rothman, Abraham; Mishra, Bhuwan B.; Virani, Shumaila; Medeiros, L. Jeffrey; Luthra, Rajyalakshmi

doi:10.1016/j.jmoldx.2016.03.008

Cited by 17 publications

(18 citation statements)

References 34 publications

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“…We performed the OncoScan Formalin‐Fixed, Paraffin‐Embedded (FFPE) Assay to asses copy number and loss of heterozygosity (LOH) on the paired samples obtained from patients with SCRC. The OncoScan FFPE Assay (Affymetrix Inc) is a platform based on Molecular Inversion Probe technology which uses small amounts of DNA from FFPE samples . Genomic DNA was quantified using the Quant‐iT PicoGreen dsDNA Assay Kit (Invitrogen, P‐7589).…”

Section: Methodsmentioning

confidence: 99%

“…The OncoScan FFPE Assay (Affymetrix Inc) is a platform based on Molecular Inversion Probe technology which uses small amounts of DNA from FFPE samples. 19,20 Genomic DNA was quantified using the Quant-iT PicoGreen dsDNA Assay Kit (Invitrogen, P-7589). The OncoScan FFPE Assay Kit was used according to the manufacturer's instructions.…”

Section: Analysis Of Copy Number Alterations By Snp Array and Analysimentioning

confidence: 99%

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Redefining synchronous colorectal cancers based on tumor clonality

Perea

Garcı́a

Corchete

et al. 2018

Intl Journal of Cancer

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To analyze the possible clonal origin of a part of Synchronous colorectal cancer (SCRC), we studied 104 paired-SCRCs from 52 consecutive patients without hereditary forms of CRC. We used a Single-Nucleotide Polymorphism array to characterize the genomic profiles, and subsequently used a statistical application to define them according to clonality within the same individual. We categorized the ensuing groups according to colonic location to identify differential phenotypes. The SCRC Monoclonal group (M) (19 cases) was divided into Monosegmental (MM) and Pancolonic (MP) groups. The SCRC Polyclonal group (P) (33 cases) was also divided into Monosegmental (PM) and Pancolonic (PP), the first exhibiting preference for left colon. The MM group showed a high rate of mucinous tumors, the lowest mean-number of tumors and associated-polyps, and the worst prognosis. The MP group included the largest mean-number of associated-polyps, best prognosis and familial cancer component. The PM group seemed to be a "frontier" group. Finally, the PP group also exhibited a mucin component, the highest mean-number of tumors (4.6) compared with the mean-number of polyps (7.7), poor prognosis and sporadic cases. Most relevant differential genomic regions within M groups were gains on 1q24 and 8q24, and deletions on 1p21 and 1p23 for MM, while within P were the gains on 7q36 and deletions on 1p36 for PM. The statistical application employed seems to define clonality more accurately in SCRC -more likely to be polyclonal in origin-, and together with the tumor locations, helped us to configure a classification with prognostic and clinical value.

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Section: Methodsmentioning

confidence: 99%

Section: Analysis Of Copy Number Alterations By Snp Array and Analysimentioning

confidence: 99%

Redefining synchronous colorectal cancers based on tumor clonality

Perea

Garcı́a

Corchete

et al. 2018

Intl Journal of Cancer

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“…We circled invasive carcinoma on hematoxylin and eosin-stained slides as a visual reference and manually micro-dissected tumor tissue from consecutive unstained sections of FFPE blocks for genomic DNA extraction and purification using PicoPure DNA extraction kit (ThermoFisher Scientific) and Agencourt AMPureXP kit (Beckman Coulter, Brea, CA) [19]. DNA was quantified using Qubit DNA HS assay Kit (ThermoFisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

“…In this respect, molecular inversion probe (MIP)-based single nucleotide polymorphism microarray technology can provide high-quality genomic data and genome-wide analysis of CNA in solid tumors when only nanograms of degraded DNA are extracted from FFPE tissue [18–20]. In comparison with FISH assay, the conventional standard for detecting single biomarker status such as HER2 amplification, MIP microarray can provide accurate and quantitative assessment of copy number gain/amplification and loss for nearly 900 cancer related genes as well as copy neutral loss of heterozygosity (LOH) of genes within chromosomal segments [19, 21]. Additionally, MIP microarray can distinguish polysomy versus co-segmental amplification of genes and genomic loci that cannot be distinguished by FISH.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide copy number aberrations and HER2 and FGFR1 alterations in primary breast cancer by molecular inversion probe microarray

Chen

Singh

et al. 2017

Oncotarget

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Breast cancer remains the second leading cause of cancer-related death in women despite stratification based on standard hormonal receptor (HR) and HER2 testing. Additional prognostic markers are needed to improve breast cancer treatment. Chromothripsis, a catastrophic genome rearrangement, has been described recently in various cancer genomes and affects cancer progression and prognosis. However, little is known about chromothripsis in breast cancer. To identify novel prognostic biomarkers in breast cancer, we used molecular inversion probe (MIP) microarray to explore genome-wide copy number aberrations (CNA) and breast cancer-related gene alterations in DNA extracted from formalin-fixed paraffin-embedded tissue. We examined 42 primary breast cancers with known HR and HER2 status assessed via immunohistochemistry and FISH and analyzed MIP microarray results for correlation with standard tests and survival outcomes. Global genome-wide CNA ranged from 0.2% to 65.7%. Chromothripsis-like patterns were observed in 23/38 (61%) cases and were more prevalent in cases with =10% CNA (20/26, 77%) than in cases with <10% CNA (3/12, 25%; p<0.01). Most frequently involved chromosomal segment was 17q12-q21, the HER2 locus. Chromothripsis-like patterns involving 17q12 were observed in 8/19 (42%) of HER2-amplified tumors but not in any of the tumors without HER2 amplification (0/19; p<0.01). HER2 amplification detected by MIP microarray was 95% concordant with conventional testing (39/41). Interestingly, 21% of patients (9/42) had fibroblast growth factor receptor 1 (FGFR1)amplification and had a 460% higher risk for mortality than those without FGFR1 amplification (p<0.01). In summary, MIP microarray provided a robust assessment of genomic CNA of breast cancer.

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“…Usually a single test (for example, ERBB2 / HER2 amplification testing) or a limited panel of approximately five tests (for example, chronic lymphocytic leukemia panel, myeloma panel). Two related technologies, array comparative genomic hybridization (aCGH) and molecular inversion probe-based (MIP) array, may have more utility in the testing of solid tumors [40, 41]. …”

Section: Current Status Of Genomic and Related Informationmentioning

confidence: 99%

Integrating cancer genomic data into electronic health records

2016

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The rise of genomically targeted therapies and immunotherapy has revolutionized the practice of oncology in the last 10–15 years. At the same time, new technologies and the electronic health record (EHR) in particular have permeated the oncology clinic. Initially designed as billing and clinical documentation systems, EHR systems have not anticipated the complexity and variety of genomic information that needs to be reviewed, interpreted, and acted upon on a daily basis. Improved integration of cancer genomic data with EHR systems will help guide clinician decision making, support secondary uses, and ultimately improve patient care within oncology clinics. Some of the key factors relating to the challenge of integrating cancer genomic data into EHRs include: the bioinformatics pipelines that translate raw genomic data into meaningful, actionable results; the role of human curation in the interpretation of variant calls; and the need for consistent standards with regard to genomic and clinical data. Several emerging paradigms for integration are discussed in this review, including: non-standardized efforts between individual institutions and genomic testing laboratories; “middleware” products that portray genomic information, albeit outside of the clinical workflow; and application programming interfaces that have the potential to work within clinical workflow. The critical need for clinical-genomic knowledge bases, which can be independent or integrated into the aforementioned solutions, is also discussed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0371-3) contains supplementary material, which is available to authorized users.

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Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe–Based Single-Nucleotide Polymorphism Array

Cited by 17 publications

References 34 publications

Redefining synchronous colorectal cancers based on tumor clonality

Redefining synchronous colorectal cancers based on tumor clonality

Genome-wide copy number aberrations and HER2 and FGFR1 alterations in primary breast cancer by molecular inversion probe microarray

Integrating cancer genomic data into electronic health records

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