Cytogenetics Laboratory

Director: Lina Shao, MD, PhD, FACMG
Lab Manager: Jennifer Bergendahl B.S MT(ASCP)

Oncology Supervisor: Turquessa Brown-Krajewski, B.S., CG(ASCP)CM
Constitutional Supervisor: Lynn Knudson-Horneber, B.S.
FISH and Microarray Supervisor: Hong Xiao, Ph.D.

North Campus Research Building
2800 Plymouth Rd. Bldg. 35
Ann Arbor, MI 48109-2800




The UMHS Clinical Cytogenetics Laboratory offers comprehensive cytogenetic testing including standard chromosome analysis (karyotyping), fluorescence in situ hybridization (FISH), and cancer cytogenomic array analysis using whole-genome SNP array. Cytogenetic studies encompass inherited or constitutional disorders such as birth defects, abnormal sexual development, and infertility, as well as neoplasias which are mostly hematologic malignancies, but also some solid tumors.

For constitutional studies, many types of specimens are analyzed, including amniotic fluid, chorionic villus samples, tissue biopsies, products of conception, and peripheral blood. A standard peripheral blood constitutional analysis consists of an examination of 20 Giemsa trypsin banded (G-banding) metaphase cells. Every chromosome pair is microscopically analyzed band for band at the 550 band level of resolution, where possible, and at least two karyotypes are prepared. When chromosome analysis is requested to rule out certain conditions, such as Turner syndrome or suspected mosaicism, an additional cell count and/or special stains will be performed. FISH testing is available as an adjunct to chromosome analysis for a wide range of microdeletion syndromes, such as DiGeorge, Prader-Willi, Angelman, Smith-Magenis, Miller-Dieker, and Williams Syndromes. FISH is used to clarify chromosomal rearrangements and identify the origin of marker chromosomes. It is also used to clarify duplications identified by constitutional microarray testing.

For chromosome analysis of oncology specimens, which can include bone marrow, lymph nodes or tumor biopsies, at least 20 metaphase cells are analyzed. Over 20 FISH assays are available for assisting diagnosis and classification of malignant hematologic disorders and certain solid tumors, evaluating prognosis and monitoring remission status. For example, identification and monitoring of the BCR/ABL fusion gene in patients with chronic myelogenous leukemia or acute lymphocytic leukemia, for a new diagnosis of APL using a probe for PML/RARA, and for detecting the cryptic t(12;21) in pediatric ALL. The following FISH oncology probes are available: BCR/ABL [t(9;22)], PML/RARA [t(15;17)], RUNX1/RUNX1T1 [t(8;21)], CBFB [inv(16)/t(16;16)], MLL (11q23), MYC (8q24), IGH/CCND1 [t(11;14)], ETV6/RUNX1 [t(12;21)], FIP1L1/PDGFRA [del(4q12)], PDGFRB (5q32), FGFR1 (8p11), and CLL panel. Additional probes may also be available as clinically indicated; contact MLabs or the Cytogenetics laboratory for additional information. FFPE FISH assays for TFE3 (Xp11.2), TFEB (6p21) and ERG (21q22) are also available for classification or prognostication of kidney or prostate malignancies.

Cancer cytogenomic array analysis using Affymetrix CytoScan platform is available as complementary for chromosome analysis in myeloid malignancies with a normal karyotype. It is also recommended for all acute lymphoblast leukemia/lymphoma at diagnosis and solid tumors. The microarray detects copy number aberrations and copy neutral loss of heterozygosity. It detects small copy number aberrations that will not be detected by chromosome analysis, such as the IKZF1 deletion in ALL, MLL tandem duplication in AML, and KIAA1497-BRAF tandem duplication in pilocytic astrocytoma. Although cancer cytogenomic array is a powerful diagnostic tool for the evaluation of chromosomal copy number changes, this assay will not detect balanced chromosomal aberrations, imbalance of regions not represented on the microarray, or point mutations. A karyotype or FISH test is more appropriate when a translocation or inversion [e.g., t(8;21), t(9;22), t(15;17), inv(16)] is suspected. Also, chromosome or FISH analysis is more appropriate if a STAT result is required. The detection threshold for mosaicism is variable (20-30%), depending on the size of the segment and tissue type.

The Cytogenetics Laboratory processes greater than 4,000 specimens a year and is staffed by over 20 technologists with extensive experience in cytogenetic analysis. The directors are certified in Clinical Genetics by the American Board of Medical Genetics (ABMG). The laboratory is accredited by the College of American Pathologists (CAP) and is an approved lab for Southwest Oncology Group and Children’s Oncology Group (at this time, only University of Michigan registered patient samples are accepted).