Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers Journal Article


Authors: Girard, N.; Ostrovnaya, I.; Lau, C.; Park, B.; Ladanyi, M.; Finley, D.; Deshpande, C.; Rusch, V.; Orlow, I.; Travis, W. D.; Pao, W.; Begg, C. B.
Article Title: Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers
Abstract: Purpose: In cases of multiple non-small cell lung cancer, clinicians must decide whether patients have independent tumors or metastases and tailor treatment accordingly. Decisions are currently made using the Martini and Melamed criteria, which are mostly based on tumor location and histologic type. New genomic tools could improve the ability to assess tumor clonality. Experimental Design: We obtained fresh-frozen tumors specimens from patients who underwent surgery on at least two occasions for presumptively independent NSCLC. We did array comparative genomic hybridization (aCGH), mutational profiling of select genes, and detailed clinicopathologic review. Results: We analyzed a total of 42 tumors from 20 patients (6 patients with synchronous tumors, 14 patients with metachronous tumors, 24 potential tumor pair comparisons); 22 tumor pairs were evaluable by aCGH. Surprisingly, classification based on genomic profiling contradicted the clinicopathologic diagnosis in four (18%) of the comparisons, identifying independent primaries in one case diagnosed as metastasis and metastases in three cases diagnosed as independent primaries. Matching somatic point mutations were observed in these latter three cases. Another four tumor pairings were assigned an "equivocal" result based on aCGH; however, matching somatic point mutations were also found in these tumor pairs. None of the tumor pairs deemed independent primaries by aCGH harbored matching mutations. Conclusion: Genomic analysis can help distinguish clonal tumors from independent primaries. The development of rapid, inexpensive, and reliable molecular tools may allow for refinement of clinicopathologic criteria currently used in this setting. © 2009 American Association for Cancer Research.
Keywords: clinical article; controlled study; human tissue; retrospective studies; somatic mutation; polymorphism, single nucleotide; histopathology; cancer localization; allele; metastasis; gene expression profiling; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; mutational analysis; neoplasm metastasis; genome; dna mutational analysis; point mutation; comparative genomic hybridization; neoplasms, multiple primary; clone cells; matched-pair analysis
Journal Title: Clinical Cancer Research
Volume: 15
Issue: 16
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2009-08-15
Start Page: 5184
End Page: 5190
Language: English
DOI: 10.1158/1078-0432.ccr-09-0594
PUBMED: 19671847
PROVIDER: scopus
PMCID: PMC2892178
DOI/URL:
Notes: --- - "Cited By (since 1996): 8" - "Export Date: 30 November 2010" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Colin B Begg
    306 Begg
  2. Valerie W Rusch
    865 Rusch
  3. William Pao
    141 Pao
  4. Nicolas Gerald Girard
    17 Girard
  5. Irene Orlow
    247 Orlow
  6. David John Finley
    40 Finley
  7. Marc Ladanyi
    1328 Ladanyi
  8. Chyau-Yueh Christopher Lau
    20 Lau
  9. William D Travis
    743 Travis
  10. Bernard J Park
    263 Park