The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

Molecular assessment is critical not only to establish a diagnosis but also to allow participation in clinical trials of therapeutic treatments that are designed for a specific set of variants or variant types. An extensive diagnostic workup involving protein studies on muscle biopsy may be used to narrow the number of single genes to be tested, but many patients never are specifically diagnosed. Comprehensive approaches to expedite molecular diagnosis now include NGS-based panel testing for sequence analysis of all disease-associated genes in a single analysis. [123] [124] [125] Heritable Cancer Panel Genomic testing for familial cancer syndromes has become routine over the past 2 decades. Approximately 50 heritable cancer syndromes are recognized and are causative of 5% to 10% of all cancers. Although familial breast cancer has perhaps become the most publicly known example of testing, genes for other inherited cancer syndromes may be included in NGS multigene panels. Patients who carry a germline mutation of BRCA1 or 2 have a lifetime risk of breast cancer of 60% to 70%. The US Preventative Task Force recommends BRCA1 and 2 testing for women who have family members with breast, ovarian, fallopian tube, or peritoneal cancer or meet other criteria. 126 Numerous studies have demonstrated the psychosocial benefits of genetic counseling and testing. 126, 127 For patients who carry a germline mutation of BRCA1 or 2, surgical interventions may significantly reduce the risk of cancer or death. Contralateral mastectomy has been shown to reduce the risk of death in carriers by 48%. 128 Prophylactic salpingooophorectomy has been shown to dramatically reduce the mortality due to ovarian cancer or breast cancer in BRCA1 mutation carriers. 129 Similarly, identification of Lynch syndrome mutations can permit surveillance leading to earlier detection and marked improvement in survival in patients developing colorectal, endometrial, or ovarian cancer. 130 Although more than 2 decades have passed since sequencebased analysis of high-penetrance cancer genes has been performed, only laboratory-developed procedures have been available. Countless patients and families have benefited from the availability of these LDPs.