Molecular Pathology

The Molecular Pathology Laboratory performs a wide range of molecular testing in the disciplines of oncology, hematology, infectious disease, genetics and pharmacogenetics, and transplant monitoring.

The laboratory performs approximately 33,000 diagnostic molecular tests annually, using a variety of technologies and platforms, such as real-time polymerase chain reaction (rt-PCR), capillary gel electrophoresis, next-generation sequencing (NGS), and Luminex-bead based array.

Our laboratory strives toward excellence in clinical service, research, and education. Our mission is to:

  • Provide advanced molecular testing for disease diagnosis, predictive response to therapy, and monitoring of therapeutic response
  • Develop and evaluate latest technologies for future clinical and research applications
  • Offer comprehensive molecular training to residents and fellows

The Molecular Pathology team, led by Jane Houldsworth, PhD has extensive experience in routine clinical service, assay development, validation, implementation, and quality control. We are also in full compliance with regulations established by the Food and Drug Administration, New York State Department of Health, The Joint Commission and the College of American Pathologists.

We frequently bring in new molecular tests with proven clinical utility for diagnosing or monitoring disease or for selecting the appropriate targeted therapy. Here are recent updates to the clinical services that we offer:

50 cancer gene panel for solid tumors

We implemented Ion Torrent NGS technology for cancer gene mutation analysis for targeted cancer treatment. We extract genomic DNA from the submitted specimen and amplified by multiplex PCR of targeted sequences in 50 genes using the Ion AmpliSeq Cancer Hotspot Panel v2 kit to generate an amplicon library of 2,800 COSMIC mutations. The library is clonally amplified by emulsion PCR, enriched, and sequenced on Ion 318 or 316 chips using the IT-PGM instrument. The detection limit of this assay is 5 percent mutant alleles in a background of wild-type alleles. The assay can be used for FFPE tissue and as little as 10 ng DNA is sufficient for the test. To perform this test, we use 15 unstained slides and one H&E slide to ensure that we have enough tumor tissue. The genes included in this panel are ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAS, GNAQ, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53 and VHL. We use this test for lung cancer, colon cancer, melanoma, and glioma.

O6-methylguanine-DNA methyltransferase (MGMT) methylation assay

MGMT is a DNA repair enzyme that when expressed is associated with tumor resistance to temozolomide-based alkylating chemotherapy. Methylation of MGMT can reduce levels of protein expression and the presence of MGMT methylation correlates with improved survival in patients with high grade gliomas as well as increased to chemotherapy with alkylating agents. This test assesses the methylation of five CpG sites (74-78) in MGMT gene associated with patient response to alkylating chemotherapeutic agents. We require a minimum tumor percentage of 20 percent for accurate assessment of MGMT methylation status. Methylation levels of MGMT of more than 13 percent are reported as positive, those below 8 percent as negative, and we consider levels between 8 and 13 percent to be indeterminate.

MYD88 mutation assay

This test detects the point mutation c.794T>C in the MYD88 gene. This mutation is found in approximately 90 percent of Waldenstrom macroglobulinemia and IgM-expressing lymphoplasmacytic lymphoma. This mutation is also found in other B-cell lymphoproliferative disorders including atypical chronic lymphocytic leukemia, nodal marginal zone lymphoma (MZL), splenic MZL, and mucosa-associated lymphoid tissue-type MZL. We use rt-PCR to quantify both MYD88 L265P and wild-type alleles. We calculate the percentage of MYD88 L265P allele as a ratio of MYD88 L265P allele to the total alleles. The assay’s limit of detection is 0.2 percent MYD88 L265P allele in a wild-type background.

Since our establishment in 2001, the Molecular Pathology Laboratory continues to rapidly expand its test menu and implements three to five new tests each year. We perform approximately 33,000 diagnostic molecular tests annually.

We provide a full range of molecular test services, including the following:

  • Oncology: Quantitative BCR-ABL1 assay for chronic myelogenous leukemia, Next Generation Sequence of 50 genes for lung and colorectal carcinomas, melanoma and glioma; JAK2, calrecticulin gene, and MPL mutation analysis for myeloproliferative disorders; NPM1 and FLT3-ITD mutation for acute myeloid leukemia; B-Cell and T-Cell gene rearrangement; MYD88 L265P mutation for lymphoplasmacytic lymphoma; and MGMT methylation analysis for gliomas.
  • Genetics and pharmacogenetics: Thrombophilia including F5 c.1601G>A (p.Arg534Gln) (aka Factor V Leiden), F2 c.*97G>A (aka Factor II 20210G>A) and MTHFR C677T and A1298C mutations, hereditary hemochromatosis, celiac disease genotyping, and IL28B genotyping.
  • Infectious diseases: HPV genotyping for cervical, anal and other tissue biopsies; EBV viral load for post-transplant lymphoproliferative disorder (PTLD); and HCV genotyping.
  • Transplant monitoring: Chimerism (engraftment analysis).

To order the Molecular Tests, contact the Molecular Pathology Laboratory (X89272) or fax the requisitions to 212-427-2082. The tests can also be ordered directly via EPIC.

Our laboratory has partnered with several biotechnology companies to bring the latest technology to the clinical laboratory, such as next-generation sequencing. In addition, we have invented several nucleic acid amplification methods (e.g., RCA and RAM) in our laboratory and have licensed them to a biotechnology company. Recently, we developed a novel proteomic technology, termed Protein Pathway Array. Based on this technology, we identified several potential protein markers, which can used to predict outcome of cancer progression and metastasis.

The Molecular Pathology Laboratory emphasizes the importance of educating clinicians and training future pathologists and geneticists. Our educational activities include:

  • Offering an Accreditation Council for Graduate Medical Education-approved Molecular Genetic Pathology Fellowship training program
  • Providing molecular genetic pathology training for pathology residents at Mount Sinai and other institutions
  • Publishing extensively in the field of molecular genetic pathology


Jane Houldsworth, PhD
Professor and Director
Ext: 88192

Meenakshi Mehrotra, PhD
Associate Professor and Assistant Director
Ext: 88211

Wei Zhang, MD
Molecular Genetic Pathology Fellow
Ext: 89297
Cell: (347) 380-3789