Using genomics to differentiate multiple primaries from metastatic lung cancer
Menée à partir d'échantillons sanguins et de 76 échantillons tumoraux prélevés sur 37 patients présentant plusieurs tumeurs pulmonaires non à petites cellules, cette étude évalue, par rapport à une analyse histologique, l'utilité d'une analyse génomique, basée sur la comparaison des points de jonction de l'ADN issus de réarrangements chromosomiques, pour distinguer des métastases de tumeurs primitives
Introduction : Genomic technologies present a promising mechanism of resolving the clinical dilemma of distinguishing independent primary tumors from intrapulmonary metastases in non-small cell lung carcinoma. We evaluated the utility of discordant mapping somatic junctions from chromosomal rearrangements, in diagnosing metastatic disease compared to the current standard histological review.
Material and Methods : Mate-pair sequencing (MPseq) was performed on DNA extracted from 76 distinct tumors from 37 cases of multiple lung cancers. Discordant mapping junctions and chromosomal copy levels were assessed for each tumor. Blood derived DNA was available on 22 of these cases for germline assessments. A lung cancer NGS panel was additionally performed on tumor pairs from 17 patients.
Results : While MPseq was able to classify lineage in all tumor pairs, histological review appeared to misclassify lineage in 27% same histology tumor pair comparisons (9 of 33). Based on disagreement between the reviewing pathologists histopathological lineage was classified as indeterminate in seven cases. In two cases where pathologists agreed on a metastatic call, no shared junctions were found suggesting independent primaries. While germline junctions passing algorithmic filters were common, on average less than three were present and all had predictable structures of small focal rearrangements or transposons. Evaluation of shared chromosomal copy changes and driver mutations through a lung cancer NGS panel, while informative, were non-definitive in calling lineage in all cases.
Conclusion : The highly unique nature and prevalence of chromosomal rearrangement in lung cancers provide a useful and definitive technique for calling lineage in multifocal lung cancer.
Journal of Thoracic Oncology , article en libre accès, 2018