Gain at chromosomal region 5p15.33, containing TERT, is the most frequent genetic event in early stages of non-small cell lung cancer

Kang, Ji Un; Koo, Sun Hoe; Kwon, Gye Cheol; Park, Jong Woo; Kim, Jin Man

doi:10.1016/j.cancergencyto.2007.12.004

Cited by 166 publications

(134 citation statements)

References 24 publications

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“…The top four predicted targets with the strongest prediction scores (57) were ZDHHC11, MTCH2, DIRC2 and PEA15 (as of January 2012 according to www.microrna.org). The gene copy number of ZDHHC11 was altered in nearly half of the patients with non-small cell lung cancer (58) and bladder cancer (59). MTCH2 is a gene exhibiting highly restricted levels of gene expression variation in tumor tissues compared to non-malignant tissues (60).…”

Section: Discussionmentioning

confidence: 99%

Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling

et al. 2012

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Abstract. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the liver. Since postoperative recurrence and intrahepatic metastases occur frequently, the postoperative 5-year survival rate is low. To investigate the molecular mechanisms of HCC progression, mRNA as well as microRNA (miRNA) expression levels have been profiled in various studies. However, no previous study has comprehensively compared the expression of miRNAs in HCC patients with various clinical features using the tumor and surrounding non-tumor tissues and normal liver samples. In this study, we profiled the expression of miRNAs in tumor and non-tumor tissues from 40 HCC patients with heterogeneous pathogenesis and 6 surrounding non-tumor tissues from patients with metastatic liver cancer. To identify miRNAs specific to each disease state, we comprehensively compared the expression of miRNAs in various combinations. The results indicate that the expression of many known as well as novel miRNAs was altered in patients with the hepatitis C virus infection compared with those with the hepatitis B virus and without any virus infection. The following miRNAs were downregulated in the tumor and non-tumor tissues, and thus could serve as novel biomarkers for chronic liver diseases: miR-18b*, miR-296-5p, miR-557, miR-581, miR-625*, miR-1228, miR-1249 and miR-2116*. Similarly, miR-129*, miR-146b-3p and miR-448 are novel candidates for HCC biomarkers regardless of virus infection.

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Section: Discussionmentioning

confidence: 99%

Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling

et al. 2012

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“…Many of these aberrations have already reported in other cancer types. For instance, frequent gains at 5p13.3 and 20q11-13 have been described in early stage NSCL cancer and in colorectal tumors [49,50,51], suggesting a potential role of these as a first step in tumor progression. In addition, gains at chr 7p22, 9q22.3, and Xq28 have been already described in other early-stage cancers [50,52,53,54,55].…”

Section: Alterations Suggestive For An Adenoma-carcinoma Sequence (Simentioning

confidence: 99%

Single nucleotide polymorphism array profiling of adrenocortical tumors: evidence for an adenoma carcinoma sequence?

Rabascio¹,

Sbiera²,

Leich³

et al. 2013

EJEA

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Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-resolution single nucleotide polymorphism arrays (Affymetrix) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH). Genomic clustering showed good separation between adenomas and carcinomas, with best partition including only chromosome 5, which was highly amplified in 17/22 malignant tumors. The malignant tumors had more relevant genomic aberrations than benign tumors, such as a higher median number of recurrent CNA (2631 vs 94), CNAs >100 Kb (62.5 vs 7) and CN losses (72.5 vs 5.5), and a higher percentage of samples with cnLOH (91% vs 29%). Within the carcinoma cohort, a precise genetic pattern (i.e. large gains at chr 5, 7, 12, and 19, and losses at chr 1, 2, 13, 17, and 22) was associated with a better prognosis (overall survival: 72.2 vs 35.4 months, P=0.063). Interestingly, >70% of gains frequent in beningn were also present in malignant tumors. Notch signaling was the most frequently involved pathway in both tumor entities. Finally, a CN gain at imprinted "IGF2" locus chr 11p15.5 appeared to be an early alteration in a multi-step tumor progression, followed by the loss of one or two alleles, associated with increased IGF2 expression, only in carcinomas. Our study serves as database for the identification of genes and pathways, such as Notch signaling, which could be involved in the pathogenesis of adrenocortical tumors. Using these data, we postulate an adenoma-carcinoma sequence for these tumors.

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“…In addition, 5p15.33 was recently identified as a susceptibility region for lung cancer, where the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes are located (Kang et al, 2008;McKay et al, 2008;Wang et al, 2008;Jin et al, 2009;Rafnar et al, 2009;Zienolddiny et al, 2009;Hsiung et al, 2010). TERT is a main functional subunit and key regulator of the telomerase enzyme.…”

Section: Introductionmentioning

confidence: 99%

Decreased risk of developing lung cancer in subjects carrying the CLPTM1L rs401681 (G>A) polymorphism: evidence from a meta-analysis

Zhang¹,

Zhang²,

Zhang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT.A genome-wide association study revealed that a single nucleotide polymorphism, CLPTM1L -rs401681 (G>A), located at the 5p15.33 locus was significantly associated with increased risk of various cancers; however, its association with lung cancer is currently inconclusive. In order to explore the relationship between this polymorphism and lung cancer risk more precisely, we performed a meta-analysis of eight eligible studies involving 9935 cases and 11,261 controls. The pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixedor random-effect models. Results indicated that this polymorphism was significantly associated with lung cancer risk in all genetic models (GA ). An analysis stratified by ethnicity and source of controls revealed a significantly decreased risk among European groups and population-based studies in all genetic models, and among Asian populations only in the dominant model comparison. Additionally, in a subgroup analysis by histology type, the CLPTM1L rs401681 polymorphism was found to significantly decrease the risks of both adenocarcinoma and squamous cell carcinoma of the lung in all genetic models. In conclusion, our study indicated that the CLPTM1L -rs401681 (G>A) polymorphism was significantly associated with decreased lung cancer risk, especially among European populations. Due to some minor limitations, our findings should be confirmed in further studies.

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Gain at chromosomal region 5p15.33, containing TERT, is the most frequent genetic event in early stages of non-small cell lung cancer

Cited by 166 publications

References 24 publications

Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling

Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling

Single nucleotide polymorphism array profiling of adrenocortical tumors: evidence for an adenoma carcinoma sequence?

Decreased risk of developing lung cancer in subjects carrying the CLPTM1L rs401681 (G>A) polymorphism: evidence from a meta-analysis

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