Technical Standards and Guidelines for Use of Clinical Genomic Microarray Analysis in Hematopoietic and Other Neoplastic Disorders: A Draft From a Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee

Abstract 4906

Interrogation of the genome utilizing microarray technologies (copy number array-CGH with or without single-nucleotide polymorphism (SNP) probes) allows detection of genomic gains and losses with unprecedented resolution. Array findings are increasing our knowledge of the genetic basis of hematologic and other malignancies. However, prior to the clinical use of these new analytic tools, laboratories must extensively validate multiple parameters such as their platform(s), software, methods, detection limits, and quality control metrics. The laboratory must demonstrate expertise in the performance of the test and interpretation of the results by testing numerous samples, different sample types, and samples from patients with different types of diseases; these array results should then be compared with the results obtained using the gold standard methods. A working group of the Laboratory Quality Assurance committee of the American College of Medical Genetics (ACMG), a professional organization of board-certified clinical and laboratory geneticists, has drafted technical standards and guidelines for clinical laboratories that intend to offer clinical testing using these technologies.

The ACMG Technical Standards and Guidelines provide support for clinical laboratory geneticists to help them provide quality laboratory genetic services. The guidelines discuss array design, selection and coverage of the genomic microarray platforms, manufacturer's premarket analytical validation recommendations (assay performance characteristics, quality parameters, and software specifications), laboratory validation recommendations for each neoplastic disorder and tissue type (blood, bone marrow, and formalin-fixed paraffin-embedded tissue), quality control metrics and documentation, and methods for confirmation of the copy number aberrations (e.g., conventional cytogenetics, FISH, PCR, MLPA, or a different microarray). Data analysis, interpretation and reporting recommendations relating to clonal diversity, limitations of the assay, and the assessment of the clinical significance of array findings are included. Quality assurance guidelines address laboratory personnel training and certification, proficiency testing, and clinically appropriate turnaround times.

Clinical laboratory medical professionals with appropriate training and certification will correlate clinical and pathological information with array findings for final reporting. The ACMG Laboratory QA committee welcomes input as the draft guidelines are being formulated.