Genomic profiling of colorectal cancer with isolated lung metastasis

Abstract

Background: Metastasis is a major cause of failed colorectal cancer (CRC) treatment. While lung metastasis (LM) is observed in 10-15% of patients with CRC, the genetic mechanisms that cause CRC to metastasize to the lung remain unclear. Methods: In this study, we employed whole exome sequencing (WES) of primary CRC tumors and matched isolated LM lesions to compare their genomic profiles. Comprehensive genomic analyses of five freshly frozen primary tumor lesions, five paired LM lesions, and matched non-cancerous tissues was achieved by WES. Results: An integrated analysis of somatic mutations, somatic copy number alterations, and clonal structures revealed that genomic alterations were present in primary and metastatic CRCs with various levels of discordance, indicating substantial levels of intertumor heterogeneity. Moreover, our results suggest that the founder clone of the primary tumor was responsible for the formation of the metastatic lesion. Additionally, only a few metastasis-specific mutations were identified, suggesting that LM-promoting mutations might be pre-existing in primary tumors. Conclusions: Primary and metastatic CRC show intertumor heterogeneity; however, both lesions were founded by the same clone. These results indicate that malignant clones contributing to disease progression should be identified during the genetic prognosis of cancer metastasis.

Single-cell sequencing reveals CD133+CD44−-originating evolution and novel stemness related variants in human colorectal cancer

“…By using tissue WES of primary CRC tumors and matched lung metastasis (LM), Zhang et al. 32 found primary and LM were founded by the same clone. However, Dang et al.…”

Imaging Characteristics and Prognostic Value of Isolated Pulmonary Metastasis from Colorectal Cancer Demonstrated with18F-FDG PET/CT

“…Isolated lung metastasis is more frequently reported in CRC patients than in those with other extrathoracic malignancies [ 5 , 11 , 12 ]. It is sometimes difficult to determine whether an SPN is PLC or an isolated lung metastasis because SPLC occasionally mimics isolated lung metastasis of CRC patients [ 13 , 14 ].…”

The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis

“…Similar to CRLM, specific oncogenes are implicated in CRPM. Zhang et al [ 53 ] demonstrated through extensive genomic profiling studies of clinical samples from five CRC patients that CRPM shared clonality with primary tumors. Furthermore, 14 of 27 mutated genes identified in CRPM (i.e., KRAS , APC , and TP53 ) were also found in the primary lesion, thus suggesting that these mutations likely existed in the primary lesion itself.…”

“…Furthermore, 14 of 27 mutated genes identified in CRPM (i.e., KRAS , APC , and TP53 ) were also found in the primary lesion, thus suggesting that these mutations likely existed in the primary lesion itself. As such, the identification of these mutations in the primary tumor during diagnostic workup or on post-resection pathologic analysis may be prognostically significant [ 53 ]. While surgical resection for isolated CRPMs is the only curative option for select patients, there are no high-quality clinical-trial data to guide practice.…”