Michael Datto

Overview:

Dr. Datto is an AP/CP/MGP board certified pathologist who specializes in molecular pathology. He is the Associate Vice President for Duke University Health System Clinical Laboratories, the Vice Chair for Clinical Pathology and Medical Director for Duke University Health System Clinical Laboratories.  

In these roles, he is responsible for maintaining the standards of the College of American Pathologists and CLIA/CMS within all Clinical Laboratories at Duke.  Specifically, Dr. Datto oversees clinical testing and reporting, develops quality management systems and proficiency testing programs, provides consultation with ordering physicians, ensures educational programs, develops strategic plans that are in line with the needs of our patient population, physicians and health system leadership, coordinates research and development, ensures adequate and appropriately trained personnel, and provides profession interpretation for molecular diagnostic testing including the wide range of PCR, quantitative PCR, sequencing and FISH based tests for inherited genetic diseases, hematologic malignancies, solid tumors and infectious diseases.

Dr. Datto also serves as the chair of the Accreditation Committee (AC) for the College of American Pathologists (CAP).  The CAP is the largest accreditor of hospital based laboratories in the US and serves as a ‘deemed entity’ by the Center for Medicare Services. In his role of chair of the AC, Dr. Datto oversees the committee that makes clinical accreditation decisions for approximately 7,000 clinical domestic and international laboratories.

Finally, Dr. Datto has an active academic program developing data system to aggregate, normalize and utilize high complexity and high volume laboratory data.  Dr. Datto and his team have developed the Molecular Registry of Tumors (Mr.T); a software solution that supports clinical trials matching, engagement with the AACR GENIE Project and the Molecular Tumor Board for Duke University Health System.  The ultimate goal of this work is to ensure that the vast amount of laboratory data generated on our Duke patients can be put to use, driving better patient care, research and education.

Positions:

Associate Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Member of the Duke Human Vaccine Institute

Duke Human Vaccine Institute
School of Medicine

Education:

B.A. 1991

Johns Hopkins University

Ph.D. 1998

Duke University

M.D. 1999

Duke University

Postdoctoral Fellow, Pharmacology

Duke University

Resident, Pathology

Duke University

Grants:

Non Muscle Myosin II Contractility Putatively Regulates Scar Contracture

Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Intellectual Property Challenges for the Development of Genomic Diagnostics

Administered By
University Institutes and Centers
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Publications:

Genomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis.

Patients with non-small cell lung cancer (NSCLC) who have distant metastases have a poor prognosis. To determine which genomic factors of the primary tumor are associated with metastasis, we analyzed data from 759 patients originally diagnosed with stage I-III NSCLC as part of the AACR Project GENIE Biopharma Collaborative consortium. We found that TP53 mutations were significantly associated with the development of new distant metastases. TP53 mutations were also more prevalent in patients with a history of smoking, suggesting that these patients may be at increased risk for distant metastasis. Our results suggest that additional investigation of the optimal management of patients with early-stage NSCLC harboring TP53 mutations at diagnosis is warranted in light of their higher likelihood of developing new distant metastases.
Authors
Van Egeren, D; Kohli, K; Warner, JL; Bedard, PL; Riely, G; Lepisto, E; Schrag, D; LeNoue-Newton, M; Catalano, P; Kehl, KL; Michor, F; AACR Project GENIE Consortium represented by Shawn Sweeney,
MLA Citation
Van Egeren, Debra, et al. “Genomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis.” Sci Rep, vol. 12, no. 1, Nov. 2022, p. 19055. Pubmed, doi:10.1038/s41598-022-21448-1.
URI
https://scholars.duke.edu/individual/pub1556451
PMID
36351964
Source
pubmed
Published In
Scientific Reports
Volume
12
Published Date
Start Page
19055
DOI
10.1038/s41598-022-21448-1

Characterization of Casirivimab Plus Imdevimab, Sotrovimab, and Bamlanivimab Plus Etesevimab-Derived Interference in Serum Protein Electrophoresis and Immunofixation Electrophoresis.

BACKGROUND: Therapeutic monoclonal antibodies can be a source of assay interference in clinical serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE), producing monoclonal bands that can be misinterpreted as a monoclonal gammopathy related to a B-cell or plasma cell neoplasm. The extent to which new anti-COVID-19 monoclonal antibodies produce this interference is unknown. METHODS: Casirivimab plus imdevimab, sotrovimab, and bamlanivimab plus etesevimab were spiked into patient serum samples to evaluate for SPEP/IFE interference, to characterize the position of therapy-derived bands relative to a reference band (either combined beta band or beta 1 band, depending on instrument platform), and to confirm heavy and light chain utilization of each medication. Serum samples from patients who had recently received casirivimab plus imdevimab or sotrovimab were also evaluated for comparison. RESULTS: When spiked into serum samples, all tested anti-COVID-19 monoclonal antibodies generated interference in SPEP/IFE. Importantly, the patterns of interference differed between spiked serum samples and serum from patients who had recently received casirivimab plus imdevimab or sotrovimab. CONCLUSIONS: Imdevimab can be added to the growing list of therapeutic monoclonal antibodies that produce sustained interference in SPEP/IFE. Although casirivimab and sotrovimab also produce assay interference in vitro, these antibodies are not reliably detected in serum from recently infused patients. The value of relative band position in recognizing bands that may represent therapeutic monoclonal antibodies is also emphasized. Clinicians and laboratorians should consider therapeutic monoclonal antibody interference in diagnostic SPEP/IFE and review a patient's medication list when new or transient monoclonal bands are identified.
Authors
Scholl, AR; Korentzelos, D; Forns, TE; Brenneman, EK; Kelm, M; Datto, M; Wheeler, SE; Carlsen, ED
MLA Citation
Scholl, Ashley Rose, et al. “Characterization of Casirivimab Plus Imdevimab, Sotrovimab, and Bamlanivimab Plus Etesevimab-Derived Interference in Serum Protein Electrophoresis and Immunofixation Electrophoresis.” J Appl Lab Med, vol. 7, no. 6, Oct. 2022, pp. 1379–87. Pubmed, doi:10.1093/jalm/jfac064.
URI
https://scholars.duke.edu/individual/pub1550505
PMID
35993812
Source
pubmed
Published In
J Appl Lab Med
Volume
7
Published Date
Start Page
1379
End Page
1387
DOI
10.1093/jalm/jfac064

Automated next-generation profiling of genomic alterations in human cancers.

The lack of validated, distributed comprehensive genomic profiling assays for patients with cancer inhibits access to precision oncology treatment. To address this, we describe elio tissue complete, which has been FDA-cleared for examination of 505 cancer-related genes. Independent analyses of clinically and biologically relevant sequence changes across 170 clinical tumor samples using MSK-IMPACT, FoundationOne, and PCR-based methods reveals a positive percent agreement of >97%. We observe high concordance with whole-exome sequencing for evaluation of tumor mutational burden for 307 solid tumors (Pearson r = 0.95) and comparison of the elio tissue complete microsatellite instability detection approach with an independent PCR assay for 223 samples displays a positive percent agreement of 99%. Finally, evaluation of amplifications and translocations against DNA- and RNA-based approaches exhibits >98% negative percent agreement and positive percent agreement of 86% and 82%, respectively. These methods provide an approach for pan-solid tumor comprehensive genomic profiling with high analytical performance.
Authors
Keefer, LA; White, JR; Wood, DE; Gerding, KMR; Valkenburg, KC; Riley, D; Gault, C; Papp, E; Vollmer, CM; Greer, A; Hernandez, J; McGregor, PM; Zingone, A; Ryan, BM; Deak, K; McCall, SJ; Datto, MB; Prescott, JL; Thompson, JF; Cerqueira, GC; Jones, S; Simmons, JK; McElhinny, A; Dickey, J; Angiuoli, SV; Diaz, LA; Velculescu, VE; Sausen, M
MLA Citation
Keefer, Laurel A., et al. “Automated next-generation profiling of genomic alterations in human cancers.” Nat Commun, vol. 13, no. 1, May 2022, p. 2830. Pubmed, doi:10.1038/s41467-022-30380-x.
URI
https://scholars.duke.edu/individual/pub1521745
PMID
35595835
Source
pubmed
Published In
Nature Communications
Volume
13
Published Date
Start Page
2830
DOI
10.1038/s41467-022-30380-x

Next-Generation Sequencing Concordance Analysis of Comprehensive Solid Tumor Profiling between a Centralized Specialty Laboratory and the Decentralized Personal Genome Diagnostics elio Tissue Complete Kitted Solution.

Genomic tumor profiling by next-generation sequencing (NGS) allows for large-scale tumor testing to inform targeted cancer therapies and immunotherapies, and to identify patients for clinical trials. These tests are often underutilized in patients with late-stage solid tumors and are typically performed in centralized specialty laboratories, thereby limiting access to these complex tests. Personal Genome Diagnostics Inc., elio tissue complete NGS solution is a comprehensive DNA-to-report kitted assay and bioinformatics solution. Comparison of 147 unique specimens from >20 tumor types was performed using the elio tissue complete solution and Foundation Medicine's FoundationOne test, which is of similar size and gene content. The analytical performance of all genomic variant types was evaluated. In general, the overall mutational profile is highly concordant between the two assays, with agreement in sequence variants reported between panels demonstrating >95% positive percentage agreement for single-nucleotide variants and insertions/deletions in clinically actionable genes. Both copy number alterations and gene translocations showed 80% to 83% positive percentage agreement, whereas tumor mutation burden and microsatellite status showed a high level of concordance across a range of mutation loads and tumor types. The Personal Genome Diagnostics Inc., elio tissue complete assay is comparable to the FoundationOne test and will allow more laboratories to offer a diagnostic NGS assay in house, which will ultimately reduce time to result and increase the number of patients receiving molecular genomic profiling and personalized treatment.
Authors
Deak, KL; Jackson, JB; Valkenburg, KC; Keefer, LA; Robinson Gerding, KM; Angiuoli, SV; Datto, MB; McCall, SJ
MLA Citation
URI
https://scholars.duke.edu/individual/pub1489694
PMID
34314880
Source
pubmed
Published In
J Mol Diagn
Volume
23
Published Date
Start Page
1324
End Page
1333
DOI
10.1016/j.jmoldx.2021.07.004

Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience.

UNLABELLED: Comprehensive genomic profiling to inform targeted therapy selection is a central part of oncology care. However, the volume and complexity of alterations uncovered through genomic profiling make it difficult for oncologists to choose the most appropriate therapy for their patients. Here, we present a solution to this problem, The Molecular Registry of Tumors (MRT) and our Molecular Tumor Board (MTB). PATIENTS AND METHODS: MRT is an internally developed system that aggregates and normalizes genomic profiling results from multiple sources. MRT serves as the foundation for our MTB, a team that reviews genomic results for all Duke University Health System cancer patients, provides notifications for targeted therapies, matches patients to biomarker-driven trials, and monitors the molecular landscape of tumors at our institution. RESULTS: Among 215 patients reviewed by our MTB over a 6-month period, we identified 176 alterations associated with therapeutic sensitivity, 15 resistance alterations, and 51 alterations with potential germline implications. Of reviewed patients, 17% were subsequently treated with a targeted therapy. For 12 molecular therapies approved during the course of this work, we identified between two and 71 patients who could qualify for treatment based on retrospective MRT data. An analysis of 14 biomarker-driven clinical trials found that MRT successfully identified 42% of patients who ultimately enrolled. Finally, an analysis of 4,130 comprehensive genomic profiles from 3,771 patients revealed that the frequency of clinically significant therapeutic alterations varied from approximately 20% to 70% depending on the tumor type and sequencing test used. CONCLUSION: With robust informatics tools, such as MRT, and the right MTB structure, a precision cancer medicine program can be developed, which provides great benefit to providers and patients with cancer.
Authors
Green, MF; Bell, JL; Hubbard, CB; McCall, SJ; McKinney, MS; Riedel, JE; Menendez, CS; Abbruzzese, JL; Strickler, JH; Datto, MB
MLA Citation
URI
https://scholars.duke.edu/individual/pub1497103
PMID
34568718
Source
pubmed
Published In
Jco Precision Oncology
Volume
5
Published Date
DOI
10.1200/PO.21.00030
Associate Professor of Pathology

Contact:

Profile

https://scholars.duke.edu/person/michael.datto

Email

michael.datto@duke.edu
Dept of Pathology, Durham, NC 27710
Duke Box 3712, Durham, NC 27710