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MA 06 - Lung Cancer Biology I (ID 660)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
MA 06.11 - Distinct Mutational Landscape and Evolutionary Trajectories of Brain Metastasis and Liver Metastasis in Lung Adenocarcinoma (ID 9282)
15:45 - 17:30 | Author(s): B. Du
Distant metastases confer mainly resistance to improving the long-term survival of patients with lung cancer. The major reason was that the genetic heterogeneity and evolutionary patterns between primary tumor and their distant metastases or among distinct metastatic sites remains poorly understood. The current study aimed to depict the distinct mutational landscape of primary lung adenocarcinoma and their distant metastases (brain or liver) and reconstruct the evolutionary history of metastases.
Seventeen patients with primary lung adenocarcinoma and distant metastases [5 with primary lesion and matched brain metastases (BM), 6 with primary lesion and matched liver metastases (LM), 6 with sole BM] were included. All tissues (by either biopsy or surgical resection) and matched peripheral blood samples were collected before systemic treatment. We performed whole-exome (150×) and targeted 416-gene panel sequencing for these samples.
In the matched cases, the mutational landscape of primary lesions for BM was distinctly different from those for LM. Compared to the primary lesions, BM had the significantly different patterns of somatic genome alterations while LM had the similar ones. In six cases with sole BM, both intratumoral and intertumoral genetic homogeneity of BM were observed. By using a set of genes which were frequently found in the primary lesions, we can clearly segregate the copy number variations (CNV) pattern of patients with BM from those with LM. Moreover, when we performed the hierarchical clustering based on these genes, we saw clear segregation between BM and LM. Patients with BM had dramatically higher tumor mutational burden (TMB) than those with LM in both primary (P < 0.01) and metastatic lesions (P < 0.001). Significant differences in TMB were also observed between primary and metastatic lesions in patients with BM (P < 0.001) instead of LM (P > 0.05). Phylogenetic analysis showed that LM followed the liner progression whereas BM followed the parallel progression. In patients with sole BM, both intratumoral and intertumoral lesions have a monoclonal origin and descend from a common ‘metastatic precursor’.
The current evidence suggested that BM had distinctly different mutational landscape from LM in lung adenocarcinoma. Patients with BM had higher TMB than those with LM. BM followed the parallel progression whereas LM followed the liner progression. Intratumoral and intertumoral lesions of BM had genetic homogeneity and originated from the same precursor. These results had profound clinical implications for application of immunotherapy and improvement of prognosis in patients with lung adenocarcinoma and distant metastases.
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