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Center for Integrated Diagnostics

Providing Clinically Actionable Diagnostics to Accelerate the Adoption of Personalized Medicine

In 2005 Massachusetts General Hospital’s department of Pathology created the Molecular Diagnostics Laboratory under the direction of Dr. A. John Iafrate, M.D.-Ph.D.  The test offerings started out small; the original two tests were 1P19Q fluorescent in situ hybridization (FISH) and microsatellite instability (MSI).  The menu of tests has expanded significantly over time with the key addition of ALK FISH which functions to assist in lung cancer treatment. In 2008, Dr. Iafrate created the Translational Research Lab (TRL) in collaboration with Mass General Cancer Center. The TRL’s mission was to design a multiplex test that would simultaneously test for the top cancer mutations for all cancer types.  The resulting SNaPshot panel tests for 92 commonly mutated loci across 23 cancer genes.  In 2011, clinical molecular diagnostics was unified as the Center for Integrated Diagnostics (CID) at MGH.

The primary role of the CID is to genotypically fingerprint patient tumors across the complete spectrum of disease sites in an effort to direct molecularly-targeted therapies, thereby enhancing the efficacy of drug treatment offerings as well as supporting prospective clinical trial designs. Patient analyses are performed as CLIA-certified clinical tests and results are generated within a timeframe that allows for direct patient care decision making as well as providing the opportunity for patients whose cancers harbor susceptible genotypes to be offered the most appropriate clinical treatment. In addition, our laboratory pursues retrospective and corollary research studies to support the expansion of our genotyping profiles. To accomplish these goals, the lab utilizes a number of molecular and cellular techniques, including fluorescent in situ hybridization (FISH), qPCR, DNA sequencing, SNP-based approaches and DNA sizing analyses. The combination of these approaches allows for the detection of somatic genetic aberrations on multiple levels, including gene copy number, point mutations and small deletions and insertions.

The CID’s mission is to work across the Massachusetts General Hospital to foster development of clinical actionable diagnostics and accelerate the adoption of personalized medicine. While we have made strides in the cancer field it is our goal to expand our testing to other disciplines.

 

 

A. John Iafrate, MD, PhD

Medical Director, Center for Integrated Diagnostics
Associate in Pathology, Massachusetts General Hospital
Associate Professor in Pathology, Harvard Medical School

Dr. Iafrate is a board-certified Pathologist who joined the MGH staff in 2005 and directs Center for Integrated Diagnostics at MGH and oversees a Translational Research Laboratory that supports both Pathology and the MGH Cancer Center. He is an MD-PhD having received his dual degree from the State University of New York at Stony Brook in 2000 and was trained in Anatomic and Molecular Genetic Pathology at Brigham and Women’s Hospital. His post-doctoral work involved the discovery and description of a novel source of human genetic diversity termed copy number variation (CNV). Since arriving at MGH, he has established a cancer diagnostics lab focusing on genetic fingerprints that help guide novel targeted therapies. His laboratory launched SNAPSHOT several years ago, an assay that tests over 100 of the most common mutations in tumors. His research is focused on lung and brain tumors, and he has been closely involved in the clinical development of crizotinib and companion diagnostics in ALK-positive lung cancers.

 

Long Phi Le, MD, PhD

Assistant in Pathology, Massachusetts General Hospital

Dr. Le is a graduate of Massachusetts Institute of Technology (1999) and received his MD-PhD from the University of Alabama at Birmingham School of Medicine in 2006.  He completed his residency training in Clinical Pathology at the Massachusetts General Hospital and his Molecular Genetic Pathology Fellowship at Brigham and Women's Hospital (2010).  He joined the MGH Department of Pathology as an instructor and assistant pathologist in 2010.  His clinical and research interests in the Diagnostic Molecular Pathology Laboratory include the application of copy number analysis, next generation sequencing, and bioinformatics in molecular diagnostics.

 

Gad A. Getz, Ph.D

Director, Bioinformatics Program, Massachusetts General Hospital Cancer Center and Department of Pathology
Paul C. Zamecnik Chair of Oncology, Massachusetts General Hospital Cancer Center
Associate Professor of Pathology, Harvard Medical School
Director, Cancer Genome Computational Analysis, Broad Institute

Dr. Getz is an internationally acclaimed leader in cancer genome analysis and is pioneering widely used cancer genome analysis tools. Dr. Getz joined the MGH staff in 2013 and directs the Bioinformatics Program at the MGH Cancer Center and Department of Pathology. Getz is also the inaugural incumbent of the Paul C. Zamecnik Chair of Oncology at the MGH Cancer Center. In addition to his role at the Massachusetts General Hospital, Getz directs the Cancer Genome Computational Analysis group at the Broad Institute. He has published numerous papers in prominent journals that describe new genes and pathways involved in different tumor types. Getz received his B.S. degree in Physics and Mathematics from Hebrew University and an M.Sc. in Physics from Tel-Aviv University. He later earned a Ph.D. in Physics from the Weizmann Institute of Science in Israel. He completed his postdoctoral training at the Broad Institute of MIT and Harvard with Todd Golub, where he focused on developing computational tools and analyzing expression of miRNAs across cancer.

 

Dora Dias-Santagata, PhD, FACMG

Assistant Molecular Pathologist, Massachusetts General Hospital
Assistant Professor of Pathology, Harvard Medical School

Dr. Dias-Santagata is board-certified in Clinical Molecular Genetics and joined the MGH staff in 2007 to co-direct the Translational Research Laboratory, a mutual collaboration between the MGH Department of Pathology and the Cancer Center. She received her PhD from the Mount Sinai School of Medicine in New York (2004), and pursued post-doctoral research work at the Brigham and Women’s Hospital in Boston. She developed and co-directed the clinical implementation of SNaPshot, a pioneering tumor genotyping strategy that has been adopted by the oncology community at MGH since March 2009, to help guide therapeutic decisions. Her research efforts include the molecular characterization of rare malignancies, lung and thyroid cancers, in an effort to uncover underlying genetic driver amenable for therapeutic intervention and mechanisms of acquired resistance to therapy.

 

Darrell R. Borger, PhD

Assistant in Biology, Massachusetts General Hospital
Instructor in Medicine, Harvard Medical School

Dr. Borger received his PhD from the University of South Carolina, School of Medicine in Biomedical Science and then received post-doctoral training at the Dana-Farber Cancer Institute, where he identified basic mechanisms that drive cancer development and promote drug resistance. At MGH, he has helped develop cutting-edge clinical testing platforms that provide genetic “fingerprinting” of patient tumor tissue that is used to support a personalized approach to cancer therapy. As Director of the Translational Research Laboratory, Biomarker Unit, he is developing novel approaches that can help rationally direct patients to experimental cancer therapy trials based on an underlying tumor biomarker. Dr. Borger’s research interests also include identifying new tumor biomarkers that may expand treatment options for cancer patients and identifying mechanisms that promote drug resistance. Dr. Borger has also played a major role in developing a new website that provides disease-specific information on how tumor genotyping can direct cancer care and identify specific trials accruing patients at the MGH that that are matched to a specific cancer type or genotyping test result. (https://targetedcancercare.massgeneral.org).

 

Miguel N. Rivera, MD

Assistant Professor of Pathology, Harvard Medical School

Dr. Rivera is a board certified pathologist who directs a research laboratory at the MGH Department of Pathology and the MGH Cancer Center. He also serves as attending physician in the Center for Integrated Diagnostics at MGH. Dr. Rivera received an A.B. in Molecular Biology from Princeton University in 1996 and an M.D. from Harvard Medical School in 2001. He completed his Anatomic Pathology residency at Brigham and Women’s Hospital and a fellowship in Molecular Diagnostics at the Harvard Combined Program. During his postdoctoral fellowship, Dr. Rivera identified the tumor suppressor gene WTX which is implicated in both tumor formation and stem cell biology. His research currently focuses on the connections between cancer and normal developmental processes and on the use of genomic technologies to identify pathways that are active in tumors and that may serve as therapeutic targets.

 

Valentina Nardi, MD

Assistant in Pathology, Massachusetts General Hospital
Instructor, Harvard Medical School

Dr. Nardi received her MD degree and board certification in Hematology in Genoa, Italy. She pursued post-doctoral research in Boston, under the supervision of Dr. George Daley at Children's Hospital Boston, developing an interest and expertise in chronic myeloid leukemia, resistance to targeted therapies, and development and applications of new technologies to detect and monitor drug resistance over time. Dr. Nardi developed an interest in molecular diagnostics and went on to complete her Anatomic Pathology residency and Hematopathology fellowship at the Massachusetts General Hospital followed by a fellowship in Molecular Diagnostics at the Harvard Combined Program.

 

Jochen K Lennerz, MD, PhD

Assistant in Pathology, Center for Integrated Diagnostics, Massachusetts General Hospital
Assistant Professor of Pathology, Harvard Medical School

Dr. Lennerz is board-certified in Anatomic- and Molecular Genetic Pathology and joined the MGH Department of Pathology and Center for Integrated Diagnostics as a staff pathologist and assistant professor in 2014.  Dr. Lennerz trained as a pathologist assistant in Berlin Germany (1994) and studied both medicine and molecular medicine at the University Erlangen Germany where he also received his MD-PhD.  He did his residency training in Anatomic Pathology (2008) and a fellowship in Molecular Genetic Pathology (2009) at Washington University in St. Louis.  After completion of a two-year gastrointestinal- and liver pathology fellowship at MGH (2011), he led a research group on biomarkers in lymphoma at Ulm University Germany.  His scientific interests are biomarkers in cancer, digital pathology, and migraine/pain research.

 

Cancer Testing

SNAPSHOT Cancer GenotypingTumor development and progression rely on the active involvement of a limited set of signaling pathways; defining the genomic signatures of different tumor types has led to the development of a new generation of gene-targeted drugs.  In our laboratory, we have developed an assay which identifies these genomic signatures by detecting mutations in over 100 commonly mutated areas in cancer. The results allow for enhanced molecular sub-classification of tumors, which facilitates the selection of appropriate gene-targeted drugs and enables clinicians to identify suitable clinical trials for their patients.  The SNaPshot Cancer Genotyping assay is clinically relevant for a wide variety of cancers including lung, colon, breast, brain, pancreas, thyroid, skin, leukemia, and more.

AMP-TranslocationThis test developed by the CID utilizes next-generation sequencing (NGS) technology to identify chromosomal rearrangements with specific therapeutic implications. The test is able to detect fusion sites for all translocations identified by the current ALK, ROS1, and RET FISH tests, and provides improved genomic detail along with an enhanced capacity for unveiling unique translocations.

FISHFluorescence in situ Hybridization (FISH) detects a variety of chromosomal aberrations in cancer, including genes that have moved (translocations), duplicated genes (amplifications), and missing genes (deletions). Our laboratory offers a wide selection of FISH assays for various cancers types, including lung, colon, brain, and soft tissue. The FISH tests that we offer are ALK, ROS, RET, EGFR, MET, PDGFRA, FGFR1, HER2, EWSR1, CHOP, SYT, FKHR, 1p19q, MYC, KRAS, and PIK3CA.

Microsatellite Instability & MLH1 Promoter MethylationMicrosatellite instability or MSI can occur due to defects in DNA mismatch repair proteins, typically leading to sporadic tumorigenesis in colorectal or endometrial cancers.  Subsequent testing for MLH1 promoter methylation status aids in ruling out hereditary nonpolyposis colorectal cancer (HNPCC, or Lynch syndrome).  In our laboratory, MSI analysis is performed via molecular and immunohistochemistry techniques.

MGMT Promoter MethylationThe promoter of MGMT, which is a DNA repair gene, can sometimes be methylated or silenced, effecting tumorigenesis. In patients with glioblastoma who are treated with alkylating agents, MGMT promoter methylation has been associated with longer survival. Therefore, determining MGMT methylation status can provide valuable prognostic information and help guide the course of treatment.


Non-Cancer Testing

Microarray / aCGH- aCGH (array-based comparative genomic hybridization), a type of chromosomal microarray, is performed to detect gains or losses at the chromosome level, aiding in the diagnosis of many genetic conditions including unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), multiple congenital anomalies (MCA), Prader-Willi syndrome and Angelman syndrome.  The microarray used at the CID has been validated for the detection of copy number variations (CNVs) and uniparental disomy (UPD) to guide patient diagnosis.

HemochromatosisThe CID’s hemochromatosis panel tests for the most commonly associated mutations within the genes related to hereditary hemochromatosis.  A correlation of clinical and genetic laboratory findings is required to determine a diagnosis of hereditary hemochromatosis.  Testing is recommended for close family members of individuals diagnosed with the condition.

Chimerism AnalysisOur laboratory uses a microsatellite assay to determine the percentage of donor and/or recipient cells present in the peripheral blood or bone marrow of a patient subsequent to allogeneic bone marrow or stem cell transplant. After transplant, the relative amount of DNA that is donor versus recipient is quantified and followed over time with subsequent patient samples to provide prognostic information.


Billing and Payment 

MGH Patients:

Testing completed for MGH patients will be billed directly to thier insurance via thier medical record number.

Non-MGH Patients:

We do not bill insurance for testing performed for non-MGH patients. Our testing is performed on a pre‐pay basis, payment (or an institution’s request to be billed) needs to be present at the time of submission. The payment options available for these cases are Institutional Billing and Direct Patient Payment.

 

  • For Institutional Billing we require a note on the institution’s letter head stating that they agree to be billed for the requested testing. The note must include the patient’s name, the tests that are being requested, the full billing address, and contact telephone number for the invoice correspondence. 
  • For Direct Patient Payment we accept checks and wire transfers as payment. Checks should be made payable to MGH CID and can be sent to our mailing address. Please keep in mind the fact that payment checks will not be cashed until the testing has been started. For wire transfers you will need to contact us to obtain a reference number that corresponds for your testing. Our wire transfer information is as follows:

 

 

Bank of America/MGPO Lock Box Address:

Bank of America/MGPO

PO Box 3662

Boston, MA 02241-3662

 

Wire Payments:

Beneficiary: MGPO Main Account

Account #: 0000 5001 4677

Bank: Bank of America

Boston, MA

Routing #: 0260 09593

 

For ACH Wires:

Add: 011000138

 

For international wires:

Add Swift Code: BOFAUS3N

 

In order for us to process a request for testing we need ALL of the items listed on the Ordering Requirements Checklist. All three forms must be filled out completely and submitted along with the specimen and payment information. Incomplete paperwork will be returned.

How to Ship

We strongly recommend sending specimens via a trackable method to ensure successful delivery. Any materials sent by either standard or express mail must be protected by using proper packaging. Glass slides must be enclosed in a slide box (available through most laboratories, usually made of plastic and hold up to five slides each). The lid of the slide boxes should be taped shut and they should be enclosed in a rigid mailing container and shipped at room temperature. We suggest that all materials related to the case be shipped in the same container to ensure that they are received together. The mailing label should include a return address. 

 

Ordering Requirements Checklist

Center for Integrated Diagnostics (CID)

Jackson Building, 10th Floor
55 Fruit Street
Boston, MA 02114

Phone: 617.643.2716
Fax: 617.643.1623
Hours: Monday through Friday, 8:30 am to 5:00 pm


Mailing Address

Massachusetts General Hospital
Center for Integrated Diagnostics (CID)
Jackson Building, Floor 10
Mailstop: GRJ 1015
55 Fruit Street
Boston, MA 02114

Billing, Specimen Submission, Testing Status Questions: 617.724.1285