Clinical and Laboratory Standards Institute MM23—Molecular Diagnostic Methods for Solid Tumors (Nonhematologic Neoplasms) describes development and implementation of nucleic acid biomarker assays for accurate detection of somatic alterations, with applications to clinical decision-making for cancer patients with solid tumors. CLSI MM23 is intended for molecular diagnostic laboratory directors, industry laboratory professionals, health care professionals (including anatomic and clinical pathologists), manufacturers and developers, and regulatory and accreditation organizations. The methods and recommendations discussed in CLSI MM23 focus primarily on detection of tumor-specific (ie, somatic) genetic abnormalities that are acquired during tumorigenesis and that are distinct from normal variations in nonmalignant cells of the same tissue.

CLSI MM23-Ed2 replaces CLSI MM23-Ed1, published in 2015. Several changes were made in this edition, including: 

• Removing most of the discussion on heritable disease testing, except for a brief discussion of heritable cancer syndromes and pharmacogenetics for solid tumor therapies 

• Adding cancer biomarkers and updating nomenclature introduced into clinical practice or late phase clinical trials since the previous edition was published 

• Expanding the discussion of test development, with a focus on somatic, solid tumor testing 

• Updating methods and technologies commonly used in the molecular pathology and genetics laboratory for solid tumor testing, with an emphasis on NGS methods 

• Adding discussion of bioinformatics pipelines, computer and storage infrastructure, and related topics, with a focus on tumor NGS 

• Revising considerations for preexamination, examination, and postexamination phases of testing, with an emphasis on molecular oncology testing 

• Incorporating discussion of cell-free circulating tumor DNA assays and other liquid biopsy assays throughout the relevant subchapters 

• Expanding discussion of quality systems, with a focus on molecular oncology testing

CLSI MM23 focuses on descriptions of various technologies and method selection for specific oncology applications. It describes the development and implementation of nucleic acid biomarker assays for accurate detection of somatic alterations, with applications for clinical decision-making in oncology. The methods and recommendations discussed focus primarily on detection of tumor-specific genetic abnormalities that are acquired during tumorigenesis and that are distinct from normal variations in nonmalignant cells of the same tissue. CLSI MM23 also includes new biomarkers described for a wide variety of tumors and newer approaches with multigene panels and complex data interpretations developed since the previous edition was published. 

CLSI MM23 focuses on the underlying nucleic acid tumor markers and variants but does not examine cell-surface antigens, immunohistochemistry (IHC), or protein markers. CLSI MM23 focuses on neoplasms that are not hematopoietic or lymphoid. Other CLSI documents provide more detailed guidance on molecular testing for heritable genetics and specimen identification (CLSI MM01), molecular hematopathology (CLSI MM05), FISH (CLSI MM07), microarrays (CLSI MM12), and multiplex nucleic acid assays (CLSI MM17), Although also covered in CLSI MM23, additional details on next-generation sequencing (NGS), including multigene DNA panels, RNA sequencing, and liquid biopsy, are covered in CLSI MM09. CLSI MM23 is intended for molecular diagnostic laboratory directors, industry laboratory professionals, health care professionals (including anatomic and clinical pathologists), manufacturers and developers, and regulatory and accreditation organizations.