Gene heterogeneity in metastasis of colorectal cancer to the lung

Hou, Jiayun; Zhang, Yong; Zhu, Zhou

doi:10.1016/j.semcdb.2016.08.034

Cited by 16 publications

(11 citation statements)

References 67 publications

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“…A previous study has also demonstrated that KRAS and PIK3CA mutations are associated with the development of LuM (14). Taken together, the above evidence suggests that LuM may represent a unique molecular subtype from that of LiM in CRC patients.…”

Section: Introductionsupporting

confidence: 57%

Genetic differences between lung metastases and liver metastases from left-sided microsatellite stable colorectal cancer: next generation sequencing and clinical implications

et al. 2021

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Background: Data regarding the clinical characteristics and outcomes of lung metastases (LuM) from colorectal cancer (CRC) are different from those of liver metastases (LiM) from CRC. However, little is known about the genetic features of LuM. This study aimed to identify the different genetic characteristics of LuM and LiM from left-sided microsatellite stable CRC. Methods: Tissue samples of the primary tumors and paired metastases from 18 CRC patients with isolated LuM (LuM cohort), 18 patients with isolated LiM (LiM cohort), and 10 locally advanced CRC patients without metastases (control cohort) were selected for next-generation sequencing. Patients in the LiM cohort had matched clinicopathological characteristics with the LuM cohort. The single-nucleotide variations (SNVs), copy number variations (CNVs), pathway alterations, and tumor mutation burdens (TMBs) were also calculated and analyzed.Results: The CNV results showed that ZFHX4, GATA2, and FAM131B amplifications were more common in the metastatic cohorts than in the control cohort, while RECQL4 and FLCN amplifications were common in the controls. The LuM cohort had significantly higher proportions of HNF4A, BRD4, and U2AF1 amplification. The LuM, LiM, and control cohorts were successfully separated using pathway alteration analysis. The LuM cohort had more frequent alterations in the RTK/RAS pathway, HIPPO pathway, KRAS, and MET than the LiM group. The LuM cohort also had relatively higher TMBs than the LiM cohort.Conclusions: CNVs in primary tumors could identify patients with LuM. Targeting the HIPPO pathway or MET and immune checkpoint inhibitors (ICIs) combined with other agents might be novel therapies for LuM.

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Section: Introductionsupporting

confidence: 57%

Genetic differences between lung metastases and liver metastases from left-sided microsatellite stable colorectal cancer: next generation sequencing and clinical implications

et al. 2021

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“…The KRAS mutation may be associated with lung metastasis and prognosis in CRC patients [ 29 – 31 ]. Studies have shown that the KRAS mutation exists in approximately 40% of CRCs, which is related to the higher cumulative incidence of lung metastasis of CRC and is an independent predictor of lung metastasis [ 32 ]. EGFR inhibitors are not recommended for KRAS mutant patients [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Characteristics of Resectable Colorectal Cancer with Pulmonary Metastasis

Qiu

Peng

Wei

et al. 2022

Canadian Journal of Gastroenterology and Hepatology

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The lung is the most common extra-abdominal metastasis site of colorectal cancer (CRC). This study aimed to investigate the genetic variation of pulmonary metastases (PM) and primary tumors in resectable CRC. The clinical data of 410 patients with PM after CRC surgery and 33 paraffin-embedded tissue samples from January 2012 to July 2019 in our hospital were collected retrospectively. Next, 450-panel gene detection technologies based on next-generation sequencing (NGS) were used to analyze the changes in the gene map and the overall variation in cancer-related genes in PM and primary tumors. After quality control, 19 samples were included in the final gene analysis. The results showed that APC (89.5%), TP53 (89.5%), and KRAS (53%) were the most common mutations in PM and primary tumors, but the gene amplification variation was enriched in primary tumors (4.6% vs. 11.4%). KRAS G12D was the most common site variation of the KRAS gene in both PM and primary tumors of CRC. There was no hotspot mutation in the TP53 locus in CRC, and the TP53 mutation in the PM was consistent with that in the primary lesion. The microsatellite instability (MSI) levels of 10 patients were MSS. The mean tumor mutation burden (TMB) of the primary tumor (5.3 muts·Mb−1) was slightly higher than that of metastasis (5.0 muts·Mb−1). In our institution, the genetic characteristics of resectable PM from CRC may be highly consistent with those of the primary tumor.

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“…Studies have confirmed that the generation of acquired drug resistance is a direct consequence of primary tumor heterogeneity. Tumor heterogeneity either directly affects therapeutic targets or shapes the TME by defining transcriptomic and phenotypic profiles to influence drug resistance ( Lawson et al, 2018 ; Marusyk et al, 2020 ; Hou et al, 2017 ) to modulate progression and therapeutic responses of tumor ( McGranahan and Swanton, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Spatial Transcriptomics for Tumor Heterogeneity Analysis

Zhang

2022

Front. Genet.

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The molecular heterogeneity of cancer is one of the major causes of drug resistance that leads to treatment failure. Thus, better understanding the heterogeneity of cancer will contribute to more precise diagnosis and improved patient outcomes. Although single-cell sequencing has become an important tool for investigating tumor heterogeneity recently, it lacks the spatial information of analyzed cells. In this regard, spatial transcriptomics holds great promise in deciphering the complex heterogeneity of cancer by providing localization-indexed gene expression information. This study reviews the applications of spatial transcriptomics in the study of tumor heterogeneity, discovery of novel spatial-dependent mechanisms, tumor immune microenvironment, and matrix microenvironment, as well as the pathological classification and prognosis of cancer. Finally, future challenges and opportunities for spatial transcriptomics technology’s applications in cancer are also discussed.

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Gene heterogeneity in metastasis of colorectal cancer to the lung

Cited by 16 publications

References 67 publications

Genetic differences between lung metastases and liver metastases from left-sided microsatellite stable colorectal cancer: next generation sequencing and clinical implications

Genetic differences between lung metastases and liver metastases from left-sided microsatellite stable colorectal cancer: next generation sequencing and clinical implications

Genetic Characteristics of Resectable Colorectal Cancer with Pulmonary Metastasis

Spatial Transcriptomics for Tumor Heterogeneity Analysis

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