Molecular Diagnostics Laboratory

Clinical situations in which molecular analysis is helpful:

Lymphomas and leukemias

DNA probe analysis of immunoglobulin and T-cell receptor genes helps distinguish benign from malignant lymphoproliferations and assists in assigning B-cell versus T-cell lineage in lymphoid neoplasms.

Many leukemias and lymphomas have genetic defects that are detectable by molecular methods. For example, 85% of follicular small cleaved cell lymphomas harbor t(14;18) detectable by bcl2 gene probes. About half of mantle cell lymphomas have t(11;14) detectable with bcl1 gene probes. Nearly all small non-cleaved (Burkitt's) lymphomas harbor a myc gene translocation.

Acute promyleocytic leukemia (AML-M3)

Acute promyelocytic leukemia (AML-M3) expresses PML/RARa fusion transcripts produced as a result of t(15;17). This tumor-specific defect contributes to disease pathogenesis. It also serves as a tumor marker that is useful for initial diagnosis and for monitoring tumor burden during therapy. Affected patients are candidates for novel treatments.

Chronic myelogenous leukemia (CML)

bcr/abl, which is the molecular equivalent of the Philadelphia chromosome or t(9;22), is present in virtually all cases of CML and in about 15% of acute lymphoblastic leukemias. Some leukemias have occult t(9;22) not detectable by karyotyping but detectable by molecular methods. Sequential samples can be analyzed during therapy to identify minimal residual disease.

Epstein-Barr virus infection

Molecular detection of EBV may be helpful in these clinical situations:

  • Post-transplant lymphoproliferative disorder (PTLD).
  • Infectious mononucleosis.
  • Monitor progression or resolution of EBV-related disease by EBV viral load assay of sequential blood samples.

Deep Venous Thrombosis

Mutation of the factor V gene (at codon 506) results in resistance to activated protein C (APC), whereas prothrombin gene mutation (G20210A) increases blood levels of prothrombin. Either mutation predisposes to deep venous thrombosis. Patients with a personal history of venous thrombosis are candidates for testing.

Hereditary Hemochromatosis

Mutation of the HFE gene is associated with inherited predisposition to iron overload. Most hereditary hemochromatosis patients are homozygous for the C282Y mutation, while a minority are compound heterozygotes for C282Y and H63D mutations. Patients with high transferrin saturation (>45%), elevated serum ferritin, hepatic siderosis, or other evidence of iron overload are candidates for testing.