Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The L-myc gene was first isolated from a human small-cell lung cancer (SCLC) cell line on the basis of its amplification and sequence similarity to c-myc and N-myc. A new mechanism of L-myc activation which results from the production of rlf-L-myc fusion protein was recently reported. On the basis of our earlier observation of a rearrangement involving amplified L-myc in an SCLC cell line, ACC-LC-49, we decided to investigate this rearrangement in detail along with the structure of L-myc amplification units in five additional SCLC cell lines. We report here the identification of a novel genomic region, termed jal, which is distinct from rlf and is juxtaposed to and amplified with L-myc during the process of DNA amplification of the region encompassing L-myc. Long-range analysis using pulsed-field gel electrophoresis revealed that the amplified L-myc locus is involved in highly complex intrachromosomal rearrangements with jal and/or rlf. Our results also suggest that the simultaneous presence of rearrangements both in rlf intron 1 and in regions immediately upstream of L-myc may be necessary for the expression of rlf-L-myc chimeric transcripts.
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PMID:Complex intrachromosomal rearrangement in the process of amplification of the L-myc gene in small-cell lung cancer. 131 69

We have recently characterized a gene fusion and chimeric protein product formed by L-myc and part of a novel gene named rlf in two small-cell lung cancer (SCLC) cell lines. The rlf-L-myc fusion gene is formed by intrachromosomal rearrangements placing the regulatory region and (at least) the first exon of rlf upstream of the L-myc gene. In the characterized cases the fusion gene has also been involved in DNA amplification. Here we report on a similar in vivo rearrangement involving rlf and L-myc in a primary SCLC tumor. In addition, we have found co-amplification of L-myc and rlf without visible rearrangements in either gene in three other SCLC tumors, confirming the physical linkage of these loci.
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PMID:Rearrangement and co-amplification of L-myc and rlf in primary lung cancer. 131 99

The myc family DNA copy number of 291 specimens (183 tumors and 108 tumor cell lines) from patients with small-cell lung cancer has been reported in 15 different studies. Thirty-five of 108 (32%) cell lines from small-cell lung cancer patients have myc family DNA amplification (16 c-myc, 7 N-myc, and 12 L-myc). Thirty-seven of 183 (20%) tumors from patients with small-cell lung cancer have myc family DNA amplification (3 c-myc, 13 N-myc, and 18 L-myc). The myc family DNA copy number in tumors from patients with small-cell lung cancer is similar in the majority of sites from the same patient. The presence of myc family DNA amplification in the tumor cell line is also typically present in the tumor from the same patient. myc family DNA amplification is present in a minority of patients with small-cell lung cancer, and the data on its association with shorter survival of patients are meager at present. Future studies on the biology of the myc family in small-cell lung cancer may require use of newer technologies that can work with small tissue samples typically available at the start of therapy.
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PMID:myc family DNA amplification in tumors and tumor cell lines from patients with small-cell lung cancer. 132 35

The 5-year survival of lung cancer patients is about 30% in Japan. One of the reasons for the poor prognosis seems to be drug resistance. It has been reported that certain types of oncogenes, such as ras, myc and fos, may play an important role in drug resistance. The myc protein forms a sequence-specific DNA-binding complex with Max and may act as a transcription factor; thus, it may be possible that myc family oncogenes are involved in DNA synthesis and repair processes mediating drug resistance. We report here that L-myc oncogene may be involved in the transition from drug-sensitive to drug-resistant phenotype of a certain small cell lung cancer cell line.
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PMID:[Relationship between drug resistance and oncogenes in lung cancer cell lines]. 133 94

For further study of the correlation of L-myc restriction-fragment-length polymorphism (RFLP) and metastasis of lung cancer to lymph nodes or other organs at the time of surgery, L-myc RFLP was analyzed in 252 Japanese lung-cancer patients. A close correlation between L-myc RFLP and metastasis was confirmed in this large number of patients (p = 0.01). The correlation was particularly pronounced in cases of adenocarcinoma and squamous-cell carcinoma. Poor prognosis (additional metastases after surgery) was observed in lung-cancer patients with L-S (identified as long and short bands produced with EcoRI) and S-S type L-myc RFLP. In addition, the death rate of lung-cancer patients with the L-S and S-S types was greater than that of those with the L-L type. Lung-cancer patients of the L-S and S-S types had almost 4 times higher incidence of multiple cancer in the lung, pharynx and other organs than those with the L-L type. Our results indicate that, in patients with lung cancer, genetic disposition with respect to the L-myc gene influences the extent of metastasis, the incidence of multiple cancers and prognosis.
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PMID:Correlation of L-myc RFLP with metastasis, prognosis and multiple cancer in lung-cancer patients. 134 36

DNA amplification of cellular proto-oncogenes is a well-established and common mechanism of oncogene activation in several types of human tumors, including the rapidly fatal small-cell lung cancer (SCLC). Approximately one fourth of primary SCLC tumors contain amplified copies of one of the three myc proto-oncogenes. Occasionally DNA amplification of the myc genes is associated with DNA rearrangements. Specifically, a novel locus named rlf is often involved in intrachromosomal L-myc rearrangements in SCLC. The structurally similar rearrangements are probably due to a highly repetitive region upstream of the L-myc gene, and result in the formation of a chimeric rlf-L-myc fusion protein. The consistent finding of the rlf-L-myc rearrangement in SCLC suggests that it may provide a selective advantage to the cells harboring it.
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PMID:Amplification and rearrangement of L-myc in human small-cell lung cancer. 137 23

Proto-oncogenes (H-ras-1 and L-myc) and tumor-suppressor gene (p53) loci have been implicated in lung carcinogenesis. DNA restriction fragment length polymorphisms at these gene loci are being evaluated in a case-control study as markers predictive of risk for cancer or of prognosis when cancer is present. The cases and controls had a cigarette-smoking history of 40 or more pack years or other abnormalities in pulmonary function tests, their ages were closely matched (64 years for cases and 61 years for controls) and the ratio of Caucasians to African Americans was close to unity (cases, 0.95:1.00, controls, 1.00:0.88). The H-ras-1 gene contains an insertion deletion polymorphism. Inheritance of rare H-ras-1 alleles, defined by MspI digestion, confers a relative risk for lung cancer of 2.0 (95% confidence interval, 0.5-7.3) for Caucasians and 3.2 (0.9-11.6) for African Americans (74 cases, 67 controls). The L-myc gene sequence has a restriction site (EcoR1) polymorphism between the second and third exons. Inheritance of restriction site-present alleles was reported to confer poor prognosis (presence of lymph node metastases) in Japanese lung cancer patients. This hypothesis was tested in both case-control study subjects (56 cases, 55 controls) and additional surgical cases (40), but no evidence was found to support the hypothesis in the U.S. population. The p53 gene is a tumor-suppressor gene that can encode either a proline or an arginine in the 72nd residue. No associations was found between the minor allele (proline) and diagnosis of lung cancer (76 cases, 68 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of H-ras-1, L-myc, and p53 polymorphisms with lung cancer risk and prognosis. 148 64

Myc gene abnormalities were studied in 30 human lung cancer cell lines. N-myc gene amplification was found in an adenocarcinoma cell line, VMRC-LCD. Neither c- or L-myc gene amplifications nor K-ras codon 12, 13, 61 point mutations were observed in this tumor. Cytomorphologically the VMRC-LCD cells had positive characteristics of typical adenocarcinoma, and the carcinoembryonic antigen in the culture medium was strongly positive. N-myc gene amplification in adenocarcinoma of the lung is extremely rare, therefore we report herein on this case.
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PMID:Amplification of the N-myc oncogene in an adenocarcinoma cell line of the lung. 162 16

Chromosomal abnormalities affecting proto-oncogenes are frequently detected in human cancer. Oncogenes of the myc family are activated in several types of tumors as a result of gene amplification or chromosomal translocation. We have recently found the L-myc gene involved in a gene fusion in small-cell lung cancer (SCLC). This results in a chimeric protein with amino-terminal sequences from a novel gene named rif joined to L-myc. Here we present a preliminary structural characterization of the rlf-L-myc fusion gene, which has been found only in cells with an amplified L-myc gene. In addition, we have used somatic cell hybrids to assign the normal rlf locus to the same chromosome (chromosome 1) on which L-myc resides. Finally, we have been able to establish a physical linkage between rif and L-myc with pulsed-field gel electrophoresis. Our results demonstrate that normal rlf and L-myc genes are separated by less than 800 kb of DNA. Thus, the rlf-L-myc gene fusions are due to similar but not identical intrachromosomal rearrangements at 1p32. The presence of independent genetic lesions that cause the formation of identical chimeric rlf-L-myc proteins suggests a role for the fusion protein in the development of these tumors.
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PMID:Intrachromosomal rearrangements fusing L-myc and rlf in small-cell lung cancer. 164 86

Oncogenes of the myc family c-raf-1 and K-ras have been reported to modulate radiosensitivity. We examined the possible relationship between in vivo radiosensitivity to single-dose irradiation with 3-10 Gy, and activity of these proto-oncogenes in 2 sets of small-cell lung cancer (SCLC) xenografts, the CPH and the GLC series. CPH-54A and CPH-54B are in vitro-derived subclones of a SCLC cell line, while the GLC tumours were established as cell lines from a patient during longitudinal follow-up. Both tumours were later transferred into nude mice. CPH-54A was more sensitive to single-dose irradiation than CPH-54B, while, with respect to the 3 GLC tumours examined, GLC-16 was most sensitive, followed by GLC-14 and GLC-19. The CPH tumours expressed similar amounts of c-myc and c-raf-1 mRNA, and neither expressed N-myc or L-myc. GLC-14 expressed N-myc and c-raf-1 mRNA but no c-myc. GLC-16 and GLC-19 expressed identical amounts of c-raf-1 and high levels of c-myc mRNA, but neither expressed N-myc or L-myc. None of the tumours was mutated at codon 12 or K-ras. Our results show that SCLC xenografts with different radiosensitivity may express identical amounts of some of the proto-oncogenes reported to modulate radiosensitivity. Thus, factors other than activation of the examined proto-oncogenes must be involved in causing the differences in radiosensitivity found in the SCLC xenografts. Possible long-term effects of irradiation on proto-oncogene expression was examined in xenografts of GLC-16, following regrowth after single-dose irradiation. No long-term difference in expression of c-raf-1 or c-myc mRNA was detected between control tumours and tumours irradiated with 5 or 10 Gy.
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PMID:Radiosensitivity of small-cell lung cancer xenografts compared with activity of c-myc, N-myc, L-myc, c-raf-1 and K-ras proto-oncogenes. 165 70


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