Allelic imbalance and instability of microsatellite loci on chromosome 1p in human non-small-cell lung cancer

Gasparian, Alexander V.; Лактионов, К. К.; Belialova, M. S.-O.; Pirogova, N. A.; Tatosyan, A. G.; Zborovskaya, I. B.

doi:10.1038/bjc.1998.263

Cited by 23 publications

(17 citation statements)

References 31 publications

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“…The L-myc oncogene has been reported in 27-38% of NSCLC and has been significantly associated with advanced disease and nodal metastases, though not with overall survival (34,35). We were able to obtain a 100% informative rate for the L-myc gene using two intragenic markers-one MS and one SNPwith 41% LOH, but there was no statistically significant difference between RC and NRC.…”

Section: Discussionmentioning

confidence: 68%

Widespread Molecular Alterations Present in Stage I Non-Small Cell Lung Carcinoma Fail to Predict Tumor Recurrence

et al. 2003

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Stage I non-small cell carcinoma (NSCLC) of the lung is typically treated with surgery alone, but with a 30 to 40% recurrence rate. Prognostic factors to stratify these patients into high-and low-risk groups would be of significant clinical value, but published data are conflicting. We studied 39 Stage I NSCLC treated with resection alone, followed for a minimum of 5 years, and divided into recurrent (RC) and non-recurrent (NRC) groups (n ‫؍‬ 12 and 27, respectively). Allelic imbalance (loss of heterozygosity, LOH) involving genomic regions containing L-myc (1p32), hOGG1 (3p26), APC/MCC (5q21), c-fms (5q33.3), p53 (17p13), and DCC (18q21), and point mutational change in K-ras-2 (12p12) were studied by PCR-based microsatellite analysis and DNA sequencing. Mutations in k-ras-2 were seen in 25% and 19% of RC and NRC tumors, respectively, most frequently in adenocarcinomas. LOH in the RC and NRC respectively were 50% and 37% for L-myc, 60% and 33% for hOGG1, 60% and 50% for APC, 38% and 35% for c-fms, 78% and 75% for p53, and 17% and 45% for DCC. No statistical significance was seen comparing any of the allelic alterations with recurrence. LOH for hOGG1 and L-myc were more commonly seen in squamous cell carcinomas. Stage I NSCLC are genetically heterogeneous with respect to mutation acquisition. The approach of investigating a panel of genes for alterations can be applied to any given tumor type, and provides information on patterns of mutations/ LOH that can help us better understand the molecular biology of tumorigenesis.KEY WORDS: Loss of heterozygosity, Non-small cell lung carcinoma, Prognosis. Mod Pathol 2003;16(1):28 -34Carcinoma of the lung is the second most frequent malignancy in men and women and the most frequent cause of cancer-related death in both sexes (31% and 25%, respectively) (1). Therapeutic intervention is based on a number of factors including the predicted outcome of the patient. The medical literature thus abounds with factors that affect prognosis, and one of the most important is stage of disease (2). Stage I lung cancer includes the TNM-based T1N0M0 and T2N0M0 tumors (3) and is typically treated with surgical resection alone. However, approximately 50% of clinical Stage I and 30 -40% of pathologic Stage I patients have disease recurrence and die after surgical resection (4, 5). These data suggest that a significant number of patients may benefit from adjuvant therapy at the time of diagnosis. Several studies have therefore focused attention on patients with Stage I disease in an attempt to identify prognostic factors that will stratify these patients into high-and low-risk groups for recurrence, with variable results. The various clinical and pathological factors identified include patient performance status, tumor size, histological subtype, mitotic rate, proliferative index, tumor angiogenesis, DNA ploidy studies, and blood group expression (4, 6 -8).Overexpression of p53 and c-erb by immunohistochemistry has been determined to be an indicator of poorer outcome (7). The issue of prognosi...

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Section: Discussionmentioning

confidence: 68%

Widespread Molecular Alterations Present in Stage I Non-Small Cell Lung Carcinoma Fail to Predict Tumor Recurrence

et al. 2003

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“…This chromosome location has been identi®ed by loss of heterozygosity studies as a site of a putative tumor suppressor gene or genes for breast carcinoma, colon carcinoma, neuroblastoma, non small cell lung carcinoma, melanoma, hepatocellular carcinoma, prostate, pancreatic endocrine tumors and Wilms' tumors (Nagai et al, 1995;Praml et al, 1995;Bieche et al, 1998;Martinsson et al, 1997;Ebrahimi et al, 1999;Gasparian et al, 1998;Chen et al, 1996;Boni et al, 1998;Williamson et al, 1997;Steenman et al, 1997;Sattler et al, 1999). However, we have not been unable to detect a mutation in the two TERE1 exons in 30 TCCs/matched normal PBLs except in the RT4 bladder tumor cell line.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder

et al. 2001

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We have identi®ed a novel cDNA product designated transitional epithelial response gene (TERE1), which was localized to chromosome 1p36. The TERE1 transcript (1.5 and 3.5 kb) is present in most normal human tissues including urothelium, but was reduced or absent in the majority of muscle invasive TCC tumors (22 out of 29 cases). The open reading frame encodes a protein of 338 amino acids (MW 36.8 KD). This protein is 57% homologous to a Drosophila protein called heix. We have shown by Western blotting and immuno-histochemistry with a polyclonal antibody to a speci®c TERE1 peptide, reduced or absent staining in muscle invasive tumors. Transfection of a sense TERE1 construct resulted in an 80 ± 90% inhibition of cellular proliferation in two TCC cell lines and a lack of aneuploidy in the TERE1-transduced J82 cell line. These data suggest a potential role for this gene product in the progression of bladder cancer. Oncogene (2001) 20, 1042 ± 1051.

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“…On the contrary, SRO2 deletions significantly correlated with advanced stage of the disease and postoperative disease recurrence (Gasparian et al, 1998). These data may suggest that SRO1 and SRO2 harbor tumor-suppressor genes involved in different stages of NSCLC development (Gasparian et al, 1998). The comparison of DNA from human tumor and normal bronchial mucosa with respect to microsatellite instability and LOH on chromosome 17p, 17q, 9p, and 9q, using 10 polymorphic markers, was performed on biopsies and tissue specimens obtained from the tumor and paired normal bronchial mucosa in 20 patients with NSCLC (Froudarakis et al, 1998).…”

Section: F Microsatellite Alterationmentioning

confidence: 89%

“…Allelic losses at these regions have been compared among adenocarcinomas and squamous cell carcinomas, and no difference has been found. On the contrary, SRO2 deletions significantly correlated with advanced stage of the disease and postoperative disease recurrence (Gasparian et al, 1998). These data may suggest that SRO1 and SRO2 harbor tumor-suppressor genes involved in different stages of NSCLC development (Gasparian et al, 1998).…”

Section: F Microsatellite Alterationmentioning

confidence: 94%

“…A set of 11 microsatellite loci spanning 1p was used to examine the frequency of allelic imbalance in a panel of 58 tumors; 87.9% of 58 cases had somatic allelic loss at one or more loci tested. Two SROs have been identified: SRO1 at 1p13.1 and SRO2 at 1p32-pter (Gasparian et al, 1998). Allelic losses at these regions have been compared among adenocarcinomas and squamous cell carcinomas, and no difference has been found.…”

Section: F Microsatellite Alterationmentioning

confidence: 99%

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Pharmacogenetics of Anticancer Drug Sensitivity in Non-Small Cell Lung Cancer

et al. 2003

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Allelic imbalance and instability of microsatellite loci on chromosome 1p in human non-small-cell lung cancer

Abstract: Summary The mapping of allelic loss on the short arm of chromosome 1 has been performed in non-small-cell lung cancer. We used a set of 11

Cited by 23 publications

References 31 publications

Widespread Molecular Alterations Present in Stage I Non-Small Cell Lung Carcinoma Fail to Predict Tumor Recurrence

Widespread Molecular Alterations Present in Stage I Non-Small Cell Lung Carcinoma Fail to Predict Tumor Recurrence

Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder

Pharmacogenetics of Anticancer Drug Sensitivity in Non-Small Cell Lung Cancer

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