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Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice.
Sequist, L V; Heist, R S; Shaw, A T; Fidias, P; Rosovsky, R; Temel, J S; Lennes, I T; Digumarthy, S; Waltman, B A; Bast, E; Tammireddy, S; Morrissey, L; Muzikansky, A; Goldberg, S B; Gainor, J; Channick, C L; Wain, J C; Gaissert, H; Donahue, D M; Muniappan, A; Wright, C; Willers, H; Mathisen, D J; Choi, N C; Baselga, J; Lynch, T J; Ellisen, L W; Mino-Kenudson, M; Lanuti, M; Borger, D R; Iafrate, A J; Engelman, J A; Dias-Santagata, D.
Afiliación
  • Sequist LV; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston. Electronic address: lvsequist@partners.org.
  • Heist RS; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Shaw AT; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Fidias P; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Rosovsky R; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston; The Mass General/North Shore Cancer Center, Danvers.
  • Temel JS; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Lennes IT; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Digumarthy S; Harvard Medical School, Boston; Department of Radiology.
  • Waltman BA; Harvard Medical School, Boston.
  • Bast E; Massachusetts General Hospital Cancer Center, Boston.
  • Tammireddy S; Massachusetts General Hospital Cancer Center, Boston.
  • Morrissey L; Massachusetts General Hospital Cancer Center, Boston.
  • Muzikansky A; Harvard Medical School, Boston; Department of Biostatistics.
  • Goldberg SB; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Gainor J; Harvard Medical School, Boston; Department of Medicine.
  • Channick CL; Harvard Medical School, Boston; Division of Pulmonary and Critical Care Medicine.
  • Wain JC; Harvard Medical School, Boston; Division of Thoracic Surgery.
  • Gaissert H; Harvard Medical School, Boston; Division of Thoracic Surgery.
  • Donahue DM; Harvard Medical School, Boston; Division of Thoracic Surgery.
  • Muniappan A; Harvard Medical School, Boston; Division of Thoracic Surgery.
  • Wright C; Harvard Medical School, Boston; Division of Thoracic Surgery.
  • Willers H; Harvard Medical School, Boston; Department of Radiation Oncology, Massachusetts General Hospital, Boston.
  • Mathisen DJ; Harvard Medical School, Boston; Division of Thoracic Surgery.
  • Choi NC; Harvard Medical School, Boston; Department of Radiation Oncology, Massachusetts General Hospital, Boston.
  • Baselga J; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Lynch TJ; Yale University School of Medicine and Yale Cancer Center, New Haven.
  • Ellisen LW; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Mino-Kenudson M; Harvard Medical School, Boston; Department of Pathology, Massachusetts General Hospital, Boston, USA.
  • Lanuti M; Harvard Medical School, Boston; Division of Thoracic Surgery.
  • Borger DR; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Iafrate AJ; Harvard Medical School, Boston; Department of Pathology, Massachusetts General Hospital, Boston, USA.
  • Engelman JA; Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
  • Dias-Santagata D; Harvard Medical School, Boston; Department of Pathology, Massachusetts General Hospital, Boston, USA.
Ann Oncol ; 22(12): 2616-2624, 2011 Dec.
Article en En | MEDLINE | ID: mdl-22071650
BACKGROUND: Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care. METHODS: We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping. RESULTS: Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and ß-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy. CONCLUSIONS: Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Reacción en Cadena de la Polimerasa Multiplex / Genotipo / Neoplasias Pulmonares Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2011 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Reacción en Cadena de la Polimerasa Multiplex / Genotipo / Neoplasias Pulmonares Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2011 Tipo del documento: Article Pais de publicación: Reino Unido