Diagnostic Pathology
Clinical Cytogenetics and CytoGenomics
K.H. Ramesh, PhD
Professor, Department of Pathology
Started as a small laboratory in the early 1990s, the Clinical Cytogenetics and CytoGenomics Laboratory at Montefiore Einstein has grown to become a specialized, state-of-the-art Molecular Cytogenetics and CytoGenomics facilty directed by K. H. Ramesh, PhD, ABMGG, FACMGG, a board certified Cytogeneticist. It was among the first laboratories in the United States approved (by the New York State Department of Health) to offer Fluorescence in Situ Hybridization Analysis (FISH) for HER2 Amplification in Breast Cancer in 2000; for CytoGenomic Arrays in 2008, and for the rarer Cholangiocarcinoma in 2010. The lab continually develops new molecular tests, the most recent of which is ROS1 FISH testing for lung cancer as mandated by the National Comprehensive Cancer Network.
The laboratory’s technical and professional experience in diagnosing and reporting the most complex Cytogenetics and CytoGenomics results is unparalleled. The expertise and the wide array of Molecular Cytogenetics tests offered have drawn Institutions such as MD Anderson Cancer Center’s School of Health Professions to send their undergraduate students for out-of-state training here. Research interests encompass diverse malignant diseases, and the lab provides support for many Montefiore oncologists. Most notably, Dr. Ramesh and his team have collaborated with Dr. Amit Verma to confirm MDM2 (12q15), MDM4 (1q32.1) and PAK1 (11q13.5-11q14.1) mutations that indirectly impair the function of p53 in MDS, AML and ATLL by a second method such as FISH Analysis. Pilot studies have shown that mutations and amplifications (detected by FISH) of MDM4 and MDM2 indirectly impair the normal functioning of p53 in AML and ATLL. Treating patients harboring such mutations with a novel stapled peptide molecule would inhibit MDM4 and MDM2, thereby restoring the normal functions of p53.
Dr. Ramesh is also currently working on an IRB-approved project to establish the clinical significance and implications of HER2 Genetic Heterogeneity (GH) in Invasive Ductal Carcinoma (IDC) of the breast. FISH analysis data are being collected and correlated with patient demographics, histological tumor type and stage, IHC results, treatment regimen and morbidity to determine if HER2 –GH has an impact on treatment modality. The goal of this research is to standardize the accuracy and consistency of interpreting GH in breast tumors, and to determine whether a systematic study of outcomes among patients with HER2-GH will contribute toward reconsiderations of HER2 reporting guidelines as mandated by ASCO/CAP (2018). Dr. Ramesh believes that FISH analysis results that reveal a high percentage of HER2-GH in IDC of the breast should be considered in the reporting guideline, as a small percentage (~8%) of patients could benefit from Kinase Inhibitor Therapy, thereby increasing their chance of survival (unpublished data).
The laboratory’s ongoing mission is to continue to develop new tests and create comprehensive testing algorithms to bridge the gap(s) between Molecular Cytogenetics, Microarray Analysis and Testing by Next Generation Sequencing.