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Wan Lam
Moderator of
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MS12 - Genome Screenings (ID 75)
- Event: WCLC 2019
- Type: Mini Symposium
- Track: Biology
- Presentations: 5
- Now Available
- Moderators:Wan Lam, Julian Carretero
- Coordinates: 9/10/2019, 11:30 - 13:00, Vancouver (2003)
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MS12.01 - Circulating Biomarkers (Now Available) (ID 3506)
11:30 - 13:00 | Presenting Author(s): Caroline Dive, Caroline Dive, Caroline Dive, Caroline Dive
- Abstract
- Presentation
Abstract
I will describe ongoing studies that seek to develop circulating biomarkers for the early detection of lung cancer. We are taking a multi-assay approach to develop a blood test with sufficient sensitivity and specificity. Our efforts are supported with targeted sample collection from a cohort that are typically described as the high risk, hard to reach. Individuals are asked to attend free lung health checks in supermarket car parks in socially deprived areas of North Manchester where many are offered a low dose CT scan. This approach has allowed a paradigm shift from detection of lung cancer at stage 4 to stage 1-2 where surgery can often be offered with curative intent. Individuals are also asked to provide a blood sample for exploratory research. This approach is generating an optimal blood sample set comprising samples from individuals with a CT positive scan (a proportional of which are false positives) or a negative CT scan with full clinical follow up. I will discuss the challenges of early detection with liquid biopsies (ctDNA, CTCs and plasma proteomes) and our strategies to mitigate them.
Information from this presentation has been removed upon request of the author.
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MS12.02 - Genomic and Functional Approaches to Understanding Cancer Aneuploidy (Now Available) (ID 3507)
11:30 - 13:00 | Presenting Author(s): Alison Taylor | Author(s): Juliann Shih, Gavin Ha, Galen Gao, Xiaoyang Zhang, Ashton Berger, Andrew Cherniack, Rameen Beroukhim, Matthew Meyerson
- Abstract
- Presentation
Abstract
Aneuploidy, whole chromosome or chromosome arm copy number imbalance, is a near-universal characteristic of human cancers. We applied methods that define chromosome arm-level aneuploidy and a global cancer aneuploidy score to 10,522 tumors of 33 types in the Cancer Genome Atlas (TCGA). Aneuploidy level was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples.
Although yeast and mammalian models of whole chromosome aneuploidies have been extensively investigated, chromosome arm-level aneuploidies have rarely been modeled. Cancer subtypes are often characterized by tumor specific patterns of these arm-level copy number alterations; for example, squamous cell carcinomas (SCCs) from different tissues of origin (including lung, esophagus, and bladder) have a pattern of chromosome 3p loss and chromosome 3q gain. Our analysis of 495 lung SCCs found chromosome 3p deletion to be the most frequent genomic alteration, occurring in almost 80% of the tumors and covering the entire length of the chromosome arm. Over two-thirds of chromosome 3p genes showed significantly decreased expression in these samples.
Without models of chromosome arm-level alterations, the phenotypic effects of specific aneuploidies in cancer, such as 3p deletion, remain unknown. However, recent advances in genome engineering and targeting of endonucleases allow new approaches to generate chromosomal alterations. Here, we used the CRISPR-Cas9 system to delete one copy of chromosome 3p in vitro. We successfully isolated almost 90 clones of immortalized lung epithelial cells with deletion of the 3p arm, with 8 validated by whole genome sequencing. Consistent with patient data, expression of 3p genes was also decreased upon deletion, as well as increased expression of interferon response genes. Phenotypic characterization revealed that cells with chromosome 3p deletion initially proliferated more slowly than their siblings. These chromosome 3p deleted cells had increased G1 arrest, but did not undergo increased apoptosis or cell death. Interestingly, after several passages in culture, the proliferation defect was rescued in chromosome 3p deleted cells; genome sequencing and karyotype analyses suggested that this was the result of chromosome 3 duplication. With our cellular model of chromosome arm-level aneuploidy, we uncovered a possible selection mechanism that allows aneuploidy tolerance in vitro. We used genome engineering to model chromosome arm-level deletions, providing a robust model that will address a gap in our understanding of aneuploidy in cancer.
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MS12.03 - LC-SCRM-Japan, a Pan-Japan Genetic Secreening of Lung Cancer (Now Available) (ID 3508)
11:30 - 13:00 | Presenting Author(s): Koichi Goto
- Abstract
- Presentation
Abstract
Precision Medicine Cancer: Development of Asian Cancer Genomic Screening Platform (LC-SCRUM-Asia)
Background: Recently many actionable driver oncogenes such as EGFR, ALK, RET, ROS1, BRAF and MET have been identified in non-small cell lung cancer (NSCLC). However, most of these driver oncogenes are rare and found in only about 1-2% of lung adenocarcinomas. To develop new molecular targeted agents for rare alterations, efficient genomic screening is needed to identify patients.
Methods: A nationwide genomic screening platform (LC-SCRUM-Japan) was established to primarily screen for ALK, RET and ROS1 fusions using RT-PCR and FISH in advanced non-squamous NSCLC without EGFR mutations in February 2013. From March 2015, this project was expanded to an academic-industrial collaboration initiative with broader eligibility criteria and tumor samples were analyzed by next-generation sequencing (NGS multiplex analysis with OncomineTM Cancer Research Panel). In addition, non-squamous NSCLC regardless of EGFR mutation status and other histological type of lung cancer including squamous NSCLC and small cell lung cancer (SCLC) were enrolled. Clinical information of all patients have also been collected to generate a clinical-genomic database that enables detailed outcome analysis of the cohort.
Results: Since its inception, more than 200 Japanese hospitals participated in this project and 7739 patients were enrolled into LC-SCRUM-Japan. 776 squamous NSCLCs and 823 SCLCs were enrolled. Through this platform, many patients with rare driver oncogenes were identified for approved targeted therapies or successfully enrolled into various clinical trials that have helped develop new targeted agents. Based on our project, crizotinib and dabrafenib/trametinib were approved for ROS1 fusions and BRAF mutation positive lung cancers in Japan, respectively. From December 2017, liquid screening with Guardant 360 (LC-SCRUM-Liquid) was initiated and a large concordance study between tissue and liquid NGS analysis was performed in 2000 patients. Additionally, to identify novel biomarkers for immune checkpoint inhibitors, an immuno-oncology biomarker study (LC-SCRUM-IBIS) was conducted with 1017 patients enrolled from February 2017 to May 2018. PD-L1 assessment by IHC and whole exon sequencing was performed. The LC-SCRUM platform was recently expanded to hospitals in Taiwan and we will expand the collaboration to China and other Southeast Asia to establish an integrated Asia cancer clinical genomic database.
Conclusion:. Genomic screening in LC-SCRUM has provided clinical value by identifying patients with actionable mutations and has helped accelerate clinical development of novel agents. To continue to elevate the standard of cancer care and treatment options for patients in Asia, we are establishing a high quality platform of genomic screening technologies and a mechanism of collecting clinical data that will help elevate precision medicine and drug development in Asia.
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MS12.04 - The International Lung Cancer Consortium (ILCCO), an International Study to Identify Risk Factors for Lung Cancer Development (Now Available) (ID 3509)
11:30 - 13:00 | Presenting Author(s): Rayjean J. Hung On Behalf Of The International Lung Cancer Consortium
- Abstract
- Presentation
Abstract
Background: The International Lung Cancer Consortium (ILCCO) was established in 2004 to maximize research efficiency for lung cancer and to share comparable epidemiological and clinical data, and biological samples across studies. Since its establishment, over 70 studies have participated in the ILCCO and shared comparable clinico-epidemiological data and a subset with biological samples and genomic data. The data harmonization was conducted at the Sinai Health System in Toronto, and genomic data is managed at the Dartmouth College of Medicine/Baylor College of Medicine. In total, the ILCCO Data Repository now has epidemiological data for over 1.2 million study participants, including 100,000 lung cancer patients, and genomic data on approximately 50,000 study participants. The large-scale epidemiological and genomic data allow us to extensively study and characterize the etiological factors, including lifestyle risk factors, medical history and genomic architectures for lung cancer development.
Methods: Data submitted from all studies are systematically checked for missing values, outliers, inadmissible values, aberrant distributions and internal inconsistencies before harmonization. Common variable definitions were developed. For lifestyle risk factors and medical history, we conducted meta-analysis based on study-specific estimates, when applicable. If heterogeneities were present, random effects models were employed to account for the heterogeneity across studies. For subgroup of interests or when sample size is limited, pooled-analyses based on individual-level data were applied. When applicable, the non-linearity relationship was assessed. For genetic susceptibility of lung cancer, we investigated the genetic loci associated with lung cancer risk using log-additive model adjusted for population ancestry and account for multiple comparisons. To assess the causality of specific exposures and lung cancer risk, we applied Mendelian Randomization and mediation analytical approaches. To estimate 5-year lung cancer absolute risk, we incorporated risk factors, medical history and genetic factors based on age-specific lung cancer incidence and the competing risk.
Results: Based on 17 ILCCO studies (24,000 cases and 81,000 controls), we observed a robust association between lung cancer risk and emphysema and pneumonia, even among never smokers, and after long latency period. Based on 24 ILCCO studies, we quantified the association between family history of lung cancer and its risk by their smoking status and affected relative types. Based on 6 studies in UK, Canada, UK and New Zealand, we assessed the association between cannabis smoking and lung cancer risk by intensity, duration and cumulative exposures and by histological subtypes. We have recently completed a largest lung cancer genetic analysis based over 29,000 lung cancer cases and 56,000 controls. We identified 10 novel lung cancer susceptibility loci, in addition to the known regions, such as TERT/CLPTM1L, CHRNA5, MHC region, RAD52, CHEK2 and found specific associations mediated through mRNA expression. We helped to quantify the effect of specific genetic variant in nicotinic receptor gene on smoking cessation and age of onset. Using genetic instruments and Mendelian Randomization approach, we confirmed the association between lung cancer risk and long telomere length. Most recently, we investigated the association between impaired lung function and lung cancer risk based on UK Biobank and ILCCO OncoArray data, and we found that impaired lung function was associated with lung cancer risk in never smokers and particularly for adenocarcinoma, most likely through immune-mediated pathways. When combining all factors into an integrative risk model, we found that individuals with highly polygenic risk scores reached lung cancer screening threshold at younger age than those with average genetic risk background.
Conclusions and Future Perspectives: ILCCO provides a powerful research platform for research on lung cancer. The collaborative projects based on ILCCO have contributed to the understanding of lung cancer etiology beyond tobacco smoking. As future perspectives, ILCCO has obtained clinical prognosis data for over 50,000 lung cancer patients and will also be able to investigate factors associated with lung cancer prognosis in depth. Finally, ILCCO has built close collaborations with several lung cancer low-dose computed tomography screening programs to jointly investigate the optimal strategy for risk stratification and early detection for lung cancer.
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MS12.05 - Genomic Studies on Small Cell Lung Cancer (Now Available) (ID 3510)
11:30 - 13:00 | Presenting Author(s): Julie George
- Abstract
- Presentation
Abstract
Section not applicable
Information from this presentation has been removed upon request of the author.
Author of
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MA04 - Models and Biomarkers (ID 122)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:Montse Sanchez-Cespedes, Kwok-kin Wong
- Coordinates: 9/08/2019, 13:30 - 15:00, Interlaken (1988)
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MA04.11 - Biological and Prognostic Implications of the Long Non-Coding Transcriptome in Tumour-Infiltrating Immune Cells (Now Available) (ID 2838)
13:30 - 15:00 | Author(s): Wan Lam
- Abstract
- Presentation
Background
The lung tumour microenvironment is defined by complex infiltration patterns of immune cells which can contribute to both tumour progression and rejection. The advent of targeted immunotherapies has transformed cancer therapy, leading to durable regression even in late-stage lung tumours. Single-cell RNA sequencing and deconvolution of bulk tumour samples have provided insight into the transcriptomes of tumour-infiltrating immune populations and the regulatory networks that promote cytotoxicity and exhaustion transcriptional programs. Long non-coding RNAs (lncRNAs) have emerged as master regulators of gene expression in tumour cells, but their role in immune cells remains undercharacterized. We sought to delineate lncRNA expression profiles in healthy and lung tumour-infiltrating immune cells in order to better understand transcriptional reprogramming in tumour-infiltrating immune cells and to explore their potential as biomarkers of patient outcome and response to immunotherapy.
Method
RNAseq profiles of flow-purified adaptive and innate immune subsets were analysed for lncRNA expression, yielding 4919 expressed lncRNAs. Immune lncRNAs were then mapped to tumour and paired non-malignant lung adenocarcinoma samples (TCGA n=108, BCCA n=72) and associated with infiltrating immune populations by deconvolution and methylation-based purity scores. Associations with tumour immunogenicity were assessed by somatic mutational load and expression of tumour-associated antigens. Immune-specific expression of lncRNAs was confirmed in an external single cell RNAseq dataset of lung adenocarcinomas (n=5).
Result
We found that lncRNA expression patterns display markedly greater cell-type specificity than protein-coding genes in healthy samples, supporting their role in cell-intrinsic transcriptional regulation. 323 immune lncRNAs were differentially expressed in lung tumours compared to matched non-malignant tissue, with enriched expression of immune lncRNAs in tumours with high antigenic load. Many of these genes were positively correlated with CD45 expression and negatively correlated with tumour purity, suggestive of immune cell-restricted expression patterns. Furthermore, a substantial proportion of these genes showed decreased expression in microdissected tumour samples, suggesting that immune-derived lncRNAs may account for gene expression patterns observed in bulk tumour data. We validated these findings in a scRNAseq dataset and analysed co-expression patterns of immune lncRNAs with immune cell markers in order to identify specific immune cell phenotypes and assess the interaction of immune lncRNAs with cytotoxicity and exhaustion transcriptional networks. We identify immune lncRNAs which may regulate expression of important immune genes related to NK and CD8+ T cell cytotoxicity, as well as immune lncRNAs which predict patient outcome and response.
Conclusion
We present an atlas of lncRNAs expressed in innate and adaptive immune cells, emphasizing the multifaceted roles of lncRNAs in homeostasis and anti-tumour immunity. We highlight the potential of immune infiltrate to confound differential expression analysis of bulk tumour RNAseq data, with consideration needed for tumour purity and immune infiltration levels. Our data provide a resource that will facilitate further identification of functionally and clinically useful lncRNAs.
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MA15 - Usage of Computer and Molecular Analysis in Treatment Selection and Disease Prognostication (ID 141)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:John Le Quesne, Noriko Motoi
- Coordinates: 9/09/2019, 15:45 - 17:15, Tokyo (1982)
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MA15.11 - Establishing a Cell Sociology Platform for the Assessment of Targetable Interactions to Predict Lung Cancer Outcome (Now Available) (ID 2652)
15:45 - 17:15 | Author(s): Wan Lam
- Abstract
- Presentation
Background
The tumor microenvironment (TME) is a complex mixture of tumor epithelium, stroma and immune cells. The immune component of the TME is highly prognostic for tumor progression and patient outcome. Immune functionality, however, is often dictated by direct cell-to-cell contacts and cannot be resolved by simple metrics of cell density (for example, number of cells per mm2 or flow cytometry). For example, direct contact between CD8+ T cells and target cells is necessary for CD8+ T cell activity, and direct contact between PD1+ and PD-L1+ cells is necessary for the efficacy of immune checkpoint inhibitors. Current immunohistochemistry (IHC) techniques identify immune cell numbers and densities, but lack assessment of spatial relationships (or “cell sociology”). Here, we develop a platform to examine these direct interactions within the TME, and assess their relationship with patient outcome in two independent non-small cell lung cancer (NSCLC) cohorts.
Method
Tissue sections of primary tumors from lung adenocarcinoma (LUAD) patients with known clinical outcome were stained using 2 multiplex IHC panels: CD3/CD8/CD79a (Panel 1) and PD1/PDL1/CD8 (Panel 2). Hyperspectral image analysis determined the phenotype of all cells. Using the same IHC panels, these observations were assessed in a secondary NSCLC dataset (n=674). Deconvolution of these images was used to identify cell types, and cellular ‘neighborhoods’ were assessed using a Voronoi approach. This cohort was also profiled by for gene expression to validate immune subset fractions. We further identified other tumor features, including the presence of tertiary lymphoid organs (TLOs; transient immune structures necessary for antibody production from B cells).
Result
High density of intra-tumoral CD8+ T cells was associated with non-recurrence of tumors. However, we find that a non-random cell sociology pattern of CD8+ T cells directly surrounded by tumor cells was more significantly associated with non-recurrence compared to density alone. Monte Carlo re‐sampling analysis determined that these cell sociology patterns were non-random.
Conclusion
Hyperspectral cell sociology expands our understanding of the complex interplay between tumor cells and immune infiltrate. This technology improves our understanding of the tumour microenvironment and allows us to directly quantify interactions that dictate immune responses to cancers. Consequently, the implementation of this platform could improve predictions of responses to immunotherapy and lead to a deeper understanding of anti-tumor immunity.
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-29 - Cellular Biology Determines Ability of XIST to Act as a miRNA Sponge in Non-Small Cell Lung Cancer (ID 2631)
09:45 - 18:00 | Author(s): Wan Lam
- Abstract
Background
XIST, the female-specific lncRNA canonically involved in silencing the X chromosome, has been suggested by many studies to function as a miRNA sponge. This sponge mechanism has been suggested to affect many cancer types, including lung adenocarcinoma (LUAD). However, determination of miRNA:lncRNA interaction is largely based on sequence homology, impeding the identification of functional gene pairs. The sex-specificity of XIST provides the opportunity to study the biological relevance of these interactions. Here we take a comprehensive approach by considering factors that affect preferential regulation through XIST-miRNA sponging in LUAD.
Method
Sequencing data from 568 LUAD and non-malignant samples (304 female and 264 male) were downloaded from CancerBrowser and processed to provide gene expression for mRNAs, miRNAs, and XIST. 3’UTR sequences of all candidate genes were run through the miRanda binding prediction algorithm. Spearman’s tests were performed to identify positively correlated candidate sponged genes.
Result
To identify the best sponge-regulated candidates, we considered genes that (1) were positively correlated with XIST expression and (2) are targeted by shared miRNA with XIST, and (3) expressed in lung adenocarcinoma. This revealed a robust set 128 of genes potentially positively regulated by XIST through the sequestration of 804 shared miRNAs. As XIST is sex-specific, we compared the changes in miRNA-target gene relationships in XIST-high and XIST-low systems to identify a high-confidence set of 13 miRNA-gene pairs. In order to interact with the exclusively nuclear expressed XIST,miRNAs must also be expressed in the nucleus. We validate the nuclear presence of several of these high confidence miRNAs using RT-qPCR, confirming the co-localization required for XIST to interact with these species.
Conclusion
We use a biology-driven approach to identify genes defended from miRNA-based inhibition by the lncRNA XIST in LUAD. Importantly, we identify that the miRNAs that mediate the XIST-target gene axis are enriched in the nucleus, co-localizing with XIST in lung cancer cell models. Our results reinforce the necessary consideration of biological features in future studies of lncRNA:miRNA interactions.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-24 - Concurrent Aberrations in G2/M-Phase Transcriptional Programs and Genomic Gatekeepers Highlight Lung Cancer Predisposition in COPD Patients (Now Available) (ID 2665)
10:15 - 18:15 | Author(s): Wan Lam
- Abstract
Background
Chronic obstructive pulmonary disease (COPD) is associated with a 7-fold increased risk of lung cancer occurrence. COPD is defined by clinical symptoms and lung function measurement. It is characterized by chronic inflammation, small airway remodelling and loss as well as destruction of alveoli (emphysema). While an important lung cancer risk factor, the molecular overlap between COPD and lung cancer tumorigenesis is relatively understudied.
Method
In order to examine the commonalities between these two diseases, we first analyzed small airway epithelial gene expression profiles from 127 COPD and 140 non-COPD ever-smoker patients obtained by bronchial brushing. We performed weighted gene correlation network analysis (WGCNA) on these gene expression profiles to discover deregulated gene modules (‘metagenes’) associated with reduced lung function (Forced Expiratory Volume at 1 second, FEV1)—a clinical measure of COPD severity most robustly negatively correlated with lung cancer risk. We then assessed the preservation of these modules in two non-small cell lung cancer (NSCLC) tumour/normal data sets (lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), n= 887 tumors total). Airway and tumor patient cohorts were matched for age, gender, tumour stage, and smoking status.
Result
We discovered 10 distinct small airway expression modules, two of which were significantly negatively correlated (p < 0.05) with patient FEV1. One of these FEV1 modules was the top overall module preserved in both NSCLC subtypes. This lung cancer-FEV1 module contained 31 genes solely enriched for two related mitotic functions— G2/M phase transition (BH-p = 0.02) and mitotic roles of polo-like kinase (BH-p = 0.001, n=31). Of these, 28 genes were significantly overexpressed in both LUAD and LUSC, and mapped to a highly-clustered sub-network of 23 proteins with 465 known and in silico predicted protein-protein interactions. When tumours enriched for this lung-cancer-FEV1 gene signature were further examined, we observed a significant co-occurrence of DNA-level alterations in DNA damage associated checkpoints, specifically mutated TP53.
Conclusion
Coordinated gene expression changes associated with COPD severity measures in small airways and preserved in NSCLC tumors are enriched for G2/M phase transition genes. These genes are further disrupted in tumors, where co-occurring mutations to gate-keeper genes occur. Progression of mitosis during abnormal aneuploidy in lung tissues of COPD patients may confer increased risk of oncogenic transformation in this population, and may underlie the molecular link between COPD and lung cancer.
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P2.03-47 - Deregulation of a Novel Cis-Acting lncRNA in Non-Small Cell Lung Cancer May Control HMGA1 Expression (ID 2727)
10:15 - 18:15 | Author(s): Wan Lam
- Abstract
Background
Since the discovery of long non-coding RNAs (lncRNAs), they have been increasingly implicated in cancer-associated phenotypes. Recently, some lncRNAs have been shown to regulate the expression of neighbouring protein-coding genes, including oncogenes and tumour suppressor genes. High mobility group A1 (HMGA1) is aberrantly expressed in several aggressive cancer types, including non-small cell lung cancer (NSCLC), where high HMGA1 expression has been associated with poor overall survival and chemotherapy resistance. While HMGA1 is known to be deregulated in lung cancer, the mechanisms that mediate its expression remain unknown. These lncRNAs, known as cis-acting, may represent undiscovered therapeutic action points in cancer driving pathways.
Here we investigate the deregulation of a putative cis-acting lncRNA in NSCLC, and it’s relationship with the oncogene HMGA1.
Method
LncRNA expression was generated from RNA-sequencing data from 36 microdissected tumour and matched non-malignant tissues. Normalized sequence read counts were used to identify transcripts with significantly deregulated expression (Wilcoxon Signed-Rank Test, BH-p<0.05). Validation was performed in sequencing data obtained from The Cancer Genome Atlas (TCGA). SiRNA-mediated knockdown of lncRNA candidates were performed in a non-malignant epithelial lung cell line (BEAS-2B). Quantitative real-time PCR was used to observe the effects of lncRNA knockdown on the expression of neighbouring protein-coding genes.
Result
Our analyses identified a lncRNA neighbour to HMGA1, RP11.513I15.6, to be significantly downregulated in 2 cohorts of LUAD samples. Conversely, we found HMGA1 expression to be significantly overexpressed in LUAD tumours, and was found to be anticorrelated with RP11.513I15.6. Additionally while RP11.513I15.6 decreased with tumour stage, HMGA1 expression increased with stage. In vitro experiments demonstrated siRNA-mediated inhibition of RP11.513I15.6 in immortalized lung epithelial cells resulted in a significant increase in HMGA1 expression.
Conclusion
Our results suggest that RP11.513I15.6 is a novel cis-acting lncRNA that negatively regulates HMGA1, and may contribute mechanistically to the maintenance of lung cancer phenotypes. Further characterization of this oncogene regulatory mechanism may uncover a novel therapeutic intervention point for tumours driven by HMGA1.
