Lung cancer and the human gene for ribonucleotide reductase subunit M1 (RRM1)

Pitterle, Diana M.; Kim, Young Chul; Jolicoeur, Ethel M C; Cao, Youjia; O'Briant, Kathy; Bepler, Gerold

doi:10.1007/s003359901114

Cited by 50 publications

(27 citation statements)

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“…This provides a sound basis for the identi®cation and functional analysis of genes in the region that may play a role in the pathogenesis of lung cancer. Functional analyses by microcell-mediated chromosome transfer and clinical studies have suggested that loss of this critical region results in a more aggressive tumor phenotype (Bepler et al, 1998O'Briant et al, 1997), and analysis of two known genes, SSA/Ro52 and RRM1, has not provided evidence for mutational inactivation Pitterle et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer

Zhao

Bepler

2001

Oncogene

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Molecular, functional, and clinical analyses strongly suggest that chromosome segment 11p15.5 contains a gene involved in lung cancer pathogenesis. The critical region of allele loss is 310 kb in size. We used our contig of P1-phage arti®cial chromosome (PAC) clones together with newly identi®ed bacterial arti®cial chromosome (BAC) clones and the draft human genome sequence to complete a contiguous string of 380 407 bp. Three PAC clones that span the region were used to identify transcripts by exon trapping. Computational gene prediction algorithms were used to query the sequence for potential genes and exons. Screening for expression was performed with tissue-speci®c and cell line derived mRNA arrays. The region contains the complete SSA/Ro52 and RRM1 genes, exons 7 ± 12 of the GOK gene, and the crad pseudo-gene. A cluster of six nearly identical genes with an intact open reading frame (ORF) of 585 bp that share 75% identity with the HSPC182 gene was found. In addition, ®ve putative novel genes were identi®ed. Sequence tagged sites (STS) and polymorphic markers were used to screen 117 lung cancer cell lines for homozygous deletions and none were identi®ed. These data provide the basis for the identi®cation of a lung cancer suppressor gene on 11p15.5. Oncogene (2001) 20, 8154 ± 8164.

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Section: Discussionmentioning

confidence: 99%

“…Two genes, SSA/Ro52 and RRM1, within this minimal region of LOH have been studied for potential inactivating mutations, and none were identi®ed Pitterle et al, 1999). Few other expressed sequence tags (ESTs) and putative genes have been localized to this region .…”

Section: Introductionmentioning

confidence: 99%

Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer

Zhao

Bepler

2001

Oncogene

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“…RRM1, localised in 11p15.5, also acts as a putative tumour suppressor gene (Pitterle et al, 1999). 11p15.5, also known as LOH11A, is frequently lost in NSCLC, and loss of heterozygosity in this region has been correlated with poor survival in resected NSCLC patients (Bepler et al, 2002).…”

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confidence: 99%

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

et al. 2008

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Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2 0 ,2 0 -difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment (Po 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression (P ¼ 0.044) and overall survival (P ¼ 0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P ¼ 0.049), time to progression (9.9 vs 2.3 months; P ¼ 0.003) and overall survival (15.4 vs 3.6; P ¼ 0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy.

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“…Clinical and cell biological studies suggest that LOH is an important tumor‐suppressor gene region in lung cancer 15, 16. Moreover, RRM1 is a metastasis suppressor gene through PTEN‐regulated pathways in lung cancer 17.…”

Section: Discussionmentioning

confidence: 99%

RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>Gis associated with increased susceptibility of lung cancer in Chinese patients

Zheng

Mao

et al. 2016

Cancer Medicine

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Ribonucleotide reductase M1 (RRM1) is a crucial gene in DNA repair. Recent studies have shown that RRM1 expression can be a powerful predictor of survival or chemotherapy sensitivity in patients presenting with carcinomas who are treated with adjuvant gemcitabine‐based chemotherapy including lung cancer. However, the relationship between the single nucleotide polymorphisms (SNP) of RRM1 and the susceptibility of lung cancer to chemotherapy has not been well addressed. We detected six tag SNPs of RRM1 genotypes in a cohort of 1007 patients with primary lung cancer and 1007 age‐ and sex‐matched population controls using SNaPshot detection technology. Logistic regression, odds ratios (OR), and 95% confidence intervals were calculated to estimate lung cancer risk associated with SNP genotypes and haplotypes, after adjusting for case–control matching factors. Compared with the T/T and A/T genotype of RRM1 *151A>T, the A/A genotype had an increased risk for overall lung cancer (adjusted OR, 1.33). Additionally, the T/T+T/C genotypes of RRM1 ‐756T>C were risk factors that increased the susceptibility to lung cancer (adjusted OR 1.54, as compared with the C/C genotype). While the T/T+G/T genotypes of RRM1 ‐585T>G behaved as protective factors to increase the susceptibility to lung cancer (adjusted OR 0.44, as compared with the C/C genotype). In summary, this is the first study to systematically identify the relationship between the polymorphisms of RRM1 and individual susceptibility to lung cancer. It is anticipated that the RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>G polymorphisms will improve the predictive prognosis of lung cancer sensitivity.

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Lung cancer and the human gene for ribonucleotide reductase subunit M1 (RRM1)

Cited by 50 publications

References 20 publications

Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer

Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>Gis associated with increased susceptibility of lung cancer in Chinese patients

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