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D. Lin
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O04 - Molecular Pathology I (ID 126)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Pathology
- Presentations: 1
- Moderators:I.I. Wistuba, W.A. Cooper
- Coordinates: 10/28/2013, 10:30 - 12:00, Parkside Ballroom A, Level 1
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O04.07 - Distinguish synchronous multiple primary lung cancers from intrapulmonary metastasis by genome sequencing (ID 3193)
11:35 - 11:45 | Author(s): D. Lin
- Abstract
- Presentation
Background
Owing to use of high-resolution computed tomography (CT) scan for lung cancers, small nodules could be detected, so that more patients are identified carrying more than one lesion in lung synchronously at the time of diagnosis. Under this circumstance, precisely distinguish multiple primary lung cancers from intrapulmonary metastasis has important significance on clinical staging and appropriate therapy design.Methods
We comprehensively compared genomic aberration profiles of each tumor in the patients with multifocal pulmonary lesions, assuming that metastasis shared a certain portion of genetic aberrations with the lesion it was originated. Therefore, whole-genome/exome sequencing were applied on 15 intrapulmonary tumors that had highly similar histological diagnosis, and 1 lymph node metastasis derived from six patients with synchronous multifocal lung cancers. The somatic nucleotide variations (SNVs) detected by whole-genome/exome sequencing were validated by either mass spectrometry or the Sanger sequencing.Results
A total of 344 non-synonymous somatic point mutations were detected in whole genome sequencing analysis (3 lesions and 1 lymph node metastasis in 1 patient), corresponding to 306 unique mutation sites. Among the 70 mutations detected in the lymph node metastasis, 36 (51.4%) were also found in lesion 1 of the 3 intrapulmonary lesions, whereas no shared mutation were detected between the metastasis and either of the other two lesions. Meanwhile, there was only 1 common mutation between lesion 2 and 3, while no shared mutations were observed between lesion 1 and 2 or lesion 1 and 3. These results suggested that the metastasis was originated from lesion 1 and the 3 lesions were independent primary tumors. In whole exome sequencing analysis (12 lesions from 5 patient), among the 389 somatic non-synonymous mutations detected, we observed a similarity between each pair of tumors within one patient ranged from 0% to 5.3%, suggesting that all the lesions were independent primary tumors rather than intrapulmonary metastasis. We also reached a same conclusion when we included all somatic mutations found across the genome/exome in the analysis. These genomic abnormality profile-based diagnosis were consistent with the diagnosis based on histological examination except one lesion in patient 5, which had been considered as an intrapulmonary metastasis by histological judgment. At the same time, EGFR or KRAS mutations, which are therapy targets for adenocarcinoma in lung were detected in 7 or 3 out of the 15 tumors in 3 or 2 patients, respectively. Heterogeneity was also observed in mutation status of these two genes among different lesions in a single patient.Conclusion
Comprehensive genomic aberration profiling is powerful for identification of multiple primary lung cancers. The lymph node metastasis in the study stands as a positive control, compared with which we could tell that lesions from multifocal primary lung cancers shared too few somatic mutations to be intrapulmonary metastasis. Considering the heterogeneous mutation status of EGFR or KRAS among different tumors derived from a single patient with multifocal primary lung cancer, molecular diagnosis should be taken for each accessible lesion when targeted adjuvant therapy is under consideration.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
