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


METHODS
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.


CONCLUSIONS
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.
Girard
Nicolas
N
Pao Lab, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Ostrovnaya
Irina
I
Lau
Christopher
C
Park
Bernard
B
Ladanyi
Marc
M
Finley
David
D
Deshpande
Charuhas
C
Rusch
Valerie
V
Orlow
Irene
I
Travis
William D
WD
Pao
William
W
Begg
Colin B
CB
D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002999:Clone Cells / Q000473:pathology; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016555:Matched-Pair Analysis; D009362:Neoplasm Metastasis; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies