Background:
Chromosome breakage analysis is a test for assessing genomic instability. The most common syndrome for which this test is diagnostic is Fanconi anemia (FA). FA is characterized by bone marrow failure, increased risk for cancer, and physical abnormalities. Progressive bone marrow failure is responsible for the most significant morbidity and mortality. Clinically heterogeneous, FA individuals are at increased risk for acute myelogenous leukemia, myelodysplastic syndrome, and solid tumors of the neck, head, oral cavities, and genitourinary system. Congenital abnormalities are present in approximately 70% of FA patients and include: café au lait spots or hypopigmentation; short stature; radial ray defects; eye defects such as microphthalmia; malformations of the kidney, genitalia, heart, gastrointestinal tract, ears, and feet. Currently, 21 genes have been identified that, when mutated, can cause FA or an FA-like phenotype.
The first step in FA diagnosis is to perform a breakage analysis on peripheral blood. However, some FA patients undergo a self-correction of cells in the hematopoietic lineage, resulting in a normal blood breakage study. In such a case, breakage analysis of skin fibroblasts is necessary to detect the increased breakage and radial formation. This phenomenon is known as somatic mosaicism. Fibroblast breakage studies may also be preferable for patients with very low white blood cell counts.
*(Note: Our lab also offers a Next Generation sequencing panel and a targeted chromosomal microarray to detect changes in all FA-associated genes. Please contact our client services representatives for more information.)
Methodology:
Cells are cultured in the presence of the clastogens mitomycin C (MMC) and diepoxybutane (DEB). Metaphase chromosomes are prepared from each culture and stained with Wright stain. Fifty metaphases are scored from each culture for the presence of breaks and radial formations.
Specimen Requirements:
Blood: If white blood count (WBC) and lymphocyte percentage (%L) are normal, then 5-10 mL in a Sodium Heparin vacutainer tube or into a pre-heparinized plastic syringe (use 0.2 mL sodium heparin, 1000 unit/mL). Do NOT use lithium heparin. If WBC or %L are low, please call the lab regarding minimum specimen requirements.
Keep at room temperature and transport to laboratory as soon as possible.
Contact Client Services at (855) 535-1522 for supplies and instructions.
Test Performed (Days):
Mon-Sat
Turn Around Time:
7 – 10 Days
Shipment Sensitivity Requirements:
- Keep specimen at room temperature during transit.
- Please contact Client Services at (855) 535-1522 for shipping kits and instructions.
- Do not use the cold pack provided in the KDL shipping kit.
- Ship the specimen overnight express, using the FedEx priority overnight label provided.
- The specimen must arrive at the lab no more than 24 hours after collection.
References:
- Alter, B. and Kupfer, G. Fanconi Anemia. Gene Reviews [Internet]. Last update: November 3, 2011.http://www.ncbi.nlm.nih.gov/books/NBK1401/
- Fargo JH, Rochowski A, Giri N, Savage SA, Olson SB, Alter BP: Comparison of chromosome breakage in non-mosaic and mosaic patients with Fanconi anemia, relatives, and patients with other inherited bone failure syndromes. Cytogenet Genome Res 144:15-27, 2014. https://www.ncbi.nlm.nih.gov/pubmed/25227706
Additional Info:
After hours, please leave message at (855) 535-1522 for the on call cytogenetic technologist.