Genetic heterogeneity in patients with multiple neoplastic lung lesions: a report of three cases.
BACKGROUND
It is important to determine the relation among the various lesions in patients presenting with multiple malignant lung tumors to define the best treatment approach. A better understanding of the molecular alterations present in the different lesions may help in defining this relation.


METHODS
We performed a detailed molecular analysis of several tumor specimens obtained from three patients presenting with multiple lung lesions. Tumor specimens were analyzed for epidermal growth factor receptor (EGFR) and k-ras mutations by direct DNA sequencing. In addition, a genome-wide chromosomal copy number analysis was performed on DNA extracted from the various lesions using array-based comparative genomic hybridization.


RESULTS
In one case, a deletion of 15 base pairs in exon 19 of EGFR was present in all tumor sites analyzed. Furthermore, a similar pattern of chromosomal aberrations was observed among the various lesions, suggesting that they share the same clonal origin. In the other two cases, in contrast, we identified distinct k-ras genotypes among the various lesions from the same patient. These lesions, moreover, showed different chromosomal aberration patterns, indicating that they may have different underlying pathways of tumorigenesis.


CONCLUSIONS
Our results show that EGFR and k-ras mutation analysis, combined with chromosomal copy number profiling, can help in defining the relationship among different tumors in one patient.
Gallegos Ruiz
Mariëlle I
MI
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
van Cruijsen
Hester
H
Smit
Egbert F
EF
Grünberg
Katrien
K
Meijer
Gerrit A
GA
Rodriguez
José A
JA
Ylstra
Bauke
B
Giaccone
Giuseppe
G
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D018740:Genetic Heterogeneity; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D013964:Thyroid Neoplasms / Q000235:genetics
D066246:ErbB Receptors