bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biallelic somatic inactivation of the mismatch repair gene MLH1 in a primary skin melanoma
Authors: Castiglia Daniele , Pagani Elena , Alvino Ester , Vernole Patrizia , Marra Giancarlo , Cannavò Elda , Jiricny Josef , Zambruno Giovanna , D'Atri Stefania 
Published: April 2003

AbstractInactivation of mismatch repair (MMR) genes has been linked to the hereditary nonpolyposis colon cancer syndrome and to a subset of sporadic cancers. A phenotypic characteristic of tumors with defective MMR is microsatellite instability (MSI). Although MSI has been reported in a proportion of cutaneous melanomas, inactivation of MMR genes in this tumor type has not been detected thus far. We recently described a human melanoma cell line, PR‐Mel, and a cutaneous metastasis from the same patient, which displayed a MMR defect, and showed high MSI. Here we report that in the PR‐Mel cell line both MLH1 alleles are somatically inactivated. One allele is lost through a chromosomal deletion of the region 3p21–24, whereas the remaining allele harbors a G → A transition at position −1 of the acceptor splice site of intron 15, leading to the in‐frame skipping of exon 16. The primary melanoma of the PR patient shows loss of heterozygosity at the BAT21 microsatellite marker, located in the MLH1 gene, and does not express the MLH1 and PMS2 proteins. Moreover, it harbors the same mutation detected in the PR‐Mel cells. These results demonstrate that biallelic inactivation of MLH1 had occurred in the primary melanoma of the PR patient and suggest that disruption of MMR might have had a role in the development of the melanoma. This is the first report in which genetic defects leading to disruption of MMR function in a human melanoma have been identified. © 2003 Wiley‐Liss, Inc.
Analysis of genetic stability at the EP300 and CREBBP loci in a panel of cancer cell lines
Authors: Tillinghast Guy W. , Partee Jason , Albert Paul , Kelley Jenny M. , Burtow Kenneth H. , Kelly Kathleen 
Published: April 2003

AbstractEP300 (p300) and CREBBP (CBP) are highly related transcriptional co‐activators possessing histone acetyltransferase activity. These proteins have been implicated in coordinating numerous transcriptional responses that are important in the processes of proliferation and differentiation. A role for EP300 and CREBBP as tumor suppressors in cancer has been suggested by the fact that they are targeted by viral oncogenes; there is an increased incidence of hematologic malignancies in mice monoallelic for CREBBP; and loss, albeit at a low frequency, of both EP300 alleles in epithelial cancers has been observed. Because the level of EP300/CREBBP appears to have a critical effect on integrating certain transcriptional processes, we sought to determine whether a loss in the combined gene dosage of EP300 and CREBBP might play a role in cancer. Accordingly, we screened a panel of 103 cell lines for loss of heterozygosity and found 35 and 51% LOH for the CREBBP and EP300 loci, respectively. Concordant loss of CREBBP and EP300 was not associated with mutations in important regions of the remaining EP300 or CREBBP genes. In addition, there did not appear to be a statistically significant selection in cancer cells, stratified by various criteria, for the concordant loss of EP300 and CREBBP. We conclude that EP300 and CREBBP rarely act as classical tumor suppressors in human cancer. Published 2003 Wiley‐Liss, Inc.
Genome‐wide analysis of acute myeloid leukemia with normal karyotype reveals a unique pattern of homeobox gene expression distinct from those with translocation‐mediated fusion events
Authors: Debernardi Silvana , Lillington Debra M. , Chaplin Tracy , Tomlinson Simon , Amess John , Rohatiner Ama , Lister T. Andrew , Young Bryan D. 
Published: April 2003

AbstractGene expression profiles were determined from presentation peripheral blood and bone marrow samples of 28 patients with acute myeloid leukemia (AML). Hierarchical clustering sorted the profiles into separate groups, each representing one of the major cytogenetic classes in AML [i.e., t(8;21), t(15;17), inv(16), 11q23, and normal karyotype]. Statistical group comparison identified genes whose expression was strongly correlated with these chromosomal classes. Moreover, the normal karyotype AMLs were characterized by distinctive up‐regulation of certain members of the class I homeobox A and B gene families, implying a common underlying genetic lesion. These data reveal novel diagnostic and therapeutic targets and demonstrate the potential of microarray‐based dissection of AML. © 2003 Wiley‐Liss, Inc.
Near‐diploid and near‐triploid human sporadic colorectal adenocarcinomas differ for KRAS2 and TP53 mutational status
Authors: Giaretti Walter , Venesio Tiziana , Sciutto Andrea , Prevosto Claudia , Geido Elio , Risio Mauro 
Published: April 2003

AbstractMutations of the KRAS2 protoncogene and inactivation of the TP53 oncosuppressor gene have been suggested to contribute to chromosomal instability (CIN) and aneuploidy in colorectal cancer (CRC). Previous work has also shown that the degree of DNA ploidy [DNA index (DI)], as obtained by flow cytometry in CRC, is non‐randomly distributed and, in particular, that DI near‐diploid and near‐triploid values are well separated by a low‐probability valley region. At present, it is not known whether a relationship exists between DI and the mutational status of KRAS2 and TP53. Multiple samples obtained from 35 human sporadic CRCs have been used to provide nuclei suspensions for flow cytometric analysis and sorting of specific DI subpopulations. Sorted nuclei were then used to analyze the high‐microsatellite‐instability (MSI‐H) phenotype and the mutation spectrum of the KRAS2 and TP53 genes. A single MSI‐H case was detected. There were 6 DNA diploid (DI = 1) and 29 aneuploid (DI ≠ 1) CRCs, with the DI aneuploid cases non‐randomly subdivided in 9 near‐diploid (DI ≠ 1 and DI ≤ 1.4), 8 near‐triploid (1.4 < DI < 1.6), and 12 high‐aneuploid (DI ≥ 1.6) cases. Proximal CRCs were more often DNA diploid and near‐diploid than distal ones, and Dukes' C cases were more commonly high‐aneuploid than Dukes' B. Moreover, the incidence of mutations of the KRAS2 and TP53 genes was lowest among the DNA near‐triploid subpopulations and highest among the near‐diploid ones. We suggest that DNA near‐diploid and near‐triploid subpopulations in human sporadic CRC reflect different genetic mechanisms of CIN and have a potentially different clinical behavior. © 2003 Wiley‐Liss, Inc.
Identification of CBL, a proto‐oncogene at 11q23.3, as a novel MLL fusion partner in a patient with de novo acute myeloid leukemia
Authors: Fu Jen‐Fen , Hsu Jia‐Jong , Tang Tzung‐Chih , Shih Lee‐Yung 
Published: April 2003

AbstractWe have shown that the CBL gene at 11q23.3, telomeric to MLL, was fused to MLL in an adult patient with de novo acute myeloid leukemia (FAB‐M1). Southern blot analysis indicated that the MLL rearrangement was involved in the chromosomal abnormality. cDNA panhandle polymerase chain reaction identified the fusion transcript, in which MLL exon 6 was fused in‐frame with CBL exon 8. Long‐distance PCR amplified the genomic junction region, which involved the fusion of the 3′ portion of an Alu element in intron 6 of MLL with the 5′ portion of an Alu element in intron 7 of CBL. The absence of extensive sequence similarity at both breakpoints of MLL and CBL indicated that the recombination was not generated through homologous recombination. MLL and CBL are located between STS markers D11S939 and D11S924. Analysis of the sequence demonstrated that the transcriptional orientation of both genes at 11q23.3 is from centromere to telomere. The results of Southern blotting in conjunction with fluorescence in situ hybridization suggest that the MLL‐CBL fusion was the result of an interstitial deletion. CBL, a proto‐oncogene, functions as a negative regulator of several receptor protein–tyrosine‐kinase signaling pathways and as an adaptor protein in tyrosine phosphorylation‐dependent signaling. CBL is the second gene at 11q23.3 found to fuse with MLL. © 2003 Wiley‐Liss, Inc.
Increased expression of the LGALS3 (Galectin 3) gene in human non–small‐cell lung cancer
Authors: Yoshimura Akinobu , Gemma Akihiko , Hosoya Yoko , Komaki Eriko , Hosomi Yukio , Okano Tetsuya , Takenaka Kiyosi , Matuda Kuniko , Seike Masahiro , Uematsu Kazutsugu , Hibino Suguru , Shibuya Masahiko , Yamada Tesshi , Hirohashi Setsuo , Kudoh Shoji 
Published: April 2003

AbstractPatients with lung cancer have a poor prognosis because of the high metastatic potential of the neoplasm. Therefore, identifying new molecular targets for anti‐metastatic therapy is very important. To identify novel key factors of tumor metastasis in lung cancer, we established the gene expression profiles of two adenocarcinoma cell line variants, PC9/f9 and PC9/f14, by use of genome‐wide human cDNA microarray analysis and comparing these profiles with that of the parental cell line, PC9. The PC9/f9 and PC9/f14 cell lines were selected for analysis because of their high metastatic potential. We identified five genes in the highly metastatic cell lines that showed a significantly enhanced or reduced expression and that had not been reported to be involved in metastasis of lung cancer. One of the overexpressed genes that was identified encoded the β‐galactoside–binding protein LGALS3 (Galectin 3). LGALS3 has been reported to be overexpressed in a variety of human cancers, but not in lung cancer, and to be involved in tumor metastasis. We examined the expression of LGALS3 by use of real‐time quantitative reverse transcription–polymerase chain reaction in 38 lung cancer cell lines and in tumor tissue obtained by thoracoscopic biopsy. A population (10/30) of the non–small‐cell lung cancers examined was found to overexpress the LGALS3 gene at levels three times higher than those of normal epithelial cells. In contrast, all small‐cell lung cancers either failed to express the gene or expressed it at a very low level. The mean of the relative expression of the LGALS3 gene in non–small‐cell lung cancer (3.065 ± 3.976) was significantly higher than those of small‐cell lung cancer (0.02 ± 0.03) (P < 0.025). This is the first report of alterations of LGALS3 gene expression in lung cancer. These results, together with the previous reports on Galectin 3 function, suggest that Galectin 3 may play a role in the process of metastasis in non–small‐cell lung cancer that overexpresses Galectin 3, but not in small‐cell cancer. Accordingly, LGALS3 may be a phenotypic marker that excludes small‐cell lung cancer and may represent a novel target molecule in non–small‐cell lung cancer therapy. © 2003 Wiley‐Liss, Inc.
Complete physical map and gene content of the human NF1 tumor suppressor region in human and mouse
Authors: Jenne Dieter E. , Tinschert Sigrid , Dorschner Michael O. , Hameister Horst , Stephens Karen , Kehrer‐Sawatzki Hildegard 
Published: April 2003

AbstractDuplicon‐mediated microdeletions around the NF1 gene are frequently associated with a severe form of neurofibromatosis type I in a subgroup of patients who show an earlier onset of cutaneous neurofibromas, dysmorphic facial features, and lower IQ values. To clarify the discrepancies between published maps of the NF1 tumor‐suppressor gene region as well as the length of gaps in these assemblies and to validate the recently described tandem duplication of the human NF1 locus, we assembled a contiguous high‐density map of BAC and PAC clones from different genomic libraries. Although two WI‐12393–derived low‐copy fragments are known to occur at the proximal and distal boundaries of the 1.5‐Mb segment that is usually deleted in NF1 microdeletion patients, we identified an additional WI‐12393–related segment between the MGC13061 and the NF1 gene, which appears to trigger interstitial deletions of smaller size as observed in two patients. Moreover, we completed the genomic organization and cDNA structure of all functional genes, CYTOR4, FLJ12735, FLJ22729, CENTA2, MGC13061, NF1, OMG, EVI2B, EVI2A, KIAA1821, MGC11316, HCA66, KIAA0160, and WI‐12393, from this region. A comparison of the human map to the orthologous region on mouse chromosome 11 revealed significant differences in the number and arrangement of genes, indicating that many chromosomal breaks with partial duplications, inversions, and deletions occurred predominantly in the primate lineage. © 2003 Wiley‐Liss, Inc.
A novel fusion gene, SS18L1/SSX1, in synovial sarcoma
Authors: Storlazzi Clelia Tiziana , Mertens Fredrik , Mandahl Nils , Gisselsson David , Isaksson Margareth , Gustafson Pelle , Domanski Henryk A. , Panagopoulos Ioannis 
Published: April 2003

AbstractSynovial sarcoma is an aggressive soft tissue tumor that is characterized cytogenetically by the t(X;18)(p11;q11) translocation, resulting in fusion between the SS18 gene on chromosome 18 and one of the SSX genes on the X chromosome. The three fusion genes that have been detected thus far, SS18/SSX1, SS18/SSX2, and SS18/SSX4, account for more than 95% of the synovial sarcomas. Because SS18/SSX fusions do not seem to occur in other tumor types, and because synovial sarcomas may sometimes be difficult to distinguish from other spindle cell tumors, molecular genetic analysis has become established as an important diagnostic tool. Upon cytogenetic analysis of a soft‐tissue tumor that showed classic synovial sarcoma morphology, we detected two supernumerary marker chromosomes but no rearrangement of chromosomes X or 18. By fluorescence in situ hybridization, the marker chromosomes were shown to contain material from chromosomes X and 20, including the SSX gene cluster on the X chromosome and the SS18L1 gene, which shows strong homology with the SS18 gene, on chromosome 20. Further RT‐PCR analysis and sequencing of the amplified products revealed a novel SS18L1/SSX1 fusion transcript in which nucleotide 1216 (exon 10) of SS18L1 was fused in‐frame with nucleotide 422 (exon 6) of SSX1. Thus, the existence of genetic heterogeneity has to be taken into account when RT‐PCR is used for the diagnosis of synovial sarcoma. © 2003 Wiley‐Liss, Inc.
Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers
Authors: Tan Duan‐Jun , Chang Julia , Chen Woan‐Ling , Agress Lesley J. , Yeh Kun‐Tu , Wang Baotyan , Wong Lee‐Jun C. 
Published: April 2003

AbstractMitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis because of its high susceptibility to oxidative DNA damage and limited repair mechanisms. For investigation of the potential role of somatic mtDNA mutations in the tumorigenesis of oral cancer, we screened the occurrence of mtDNA mutations by the temporal temperature gradient gel electrophoresis method. We amplified the entire mitochondrial genome by use of 32 pairs of overlapping primers, and to identify the mutations, we sequenced DNA fragments showing different banding patterns between normal and tumor mtDNA. Fourteen of eighteen (77.8%) oral carcinomas displayed somatic mtDNA mutations, with a total of 26 mutations. Among them, six were in the mRNA coding region. Three were missense mutations (C14F, H186R, T173P) in NADH dehydrogenase subunit 2, and one was a frameshift mutation, 9485delC, in cytochrome c oxidase subunit III. Eight (44%) tumors had insertion or deletion mutations in the nucleotide position 303–309 poly C region of the D‐loop. Multiple large deletions were also observed. Our results demonstrate that somatic mtDNA mutations occur in oral cancer. Some missense and frameshift mutations may play an important role in the tumorigenesis of this carcinoma. More extensive biochemical and molecular studies will be necessary for determining the pathologic effect of these somatic mutations. © 2003 Wiley‐Liss, Inc.
Radiation therapy for recurrent orbital hemangioma
Authors: Mierzwa Michelle L. , Barrett William L. , Gluckman Jack L. 
Published: April 2003

AbstractBackground.Surgical resection and corticosteroid therapy have traditionally been the preferred methods of treatment for orbital hemangioma. Radiation therapy is not usually indicated because of the potential for ocular complications. With modern radiation techniques, however, patients may experience substantial clinical improvement without significant radiation‐induced morbidity.Methods.A case of unresectable, recurrent orbital hemangioma is described. The clinical presentation, management protocol using radiation therapy, and 5‐year follow‐up are reviewed.Results.The patient was initially seen with left orbital pain, diplopia, proptosis, and conjunctival edema caused by a recurrent left orbital hemangioma after failed previous surgery. CT scan and angiogram revealed a large, irregular, multilocular mass in the left orbit consistent with hemangioma. The patient was treated with a total of 2000 cGy in 10 treatments. Five‐year follow‐up revealed a stable, regressed hemangioma with no radiation complications.Conclusions.Radiation therapy may be used if appropriately indicated for function‐threatening orbital hemangioma. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Complications in transoral CO2 laser surgery for carcinoma of the larynx and hypopharynx
Authors: Vilaseca‐González Isabel , Bernal‐Sprekelsen Manuel , Blanch‐Alejandro José‐Luis , Moragas‐Lluis Miguel 
Published: April 2003

AbstractBackground.Because of the increase in indications for laser surgery to treat malignant tumors of the larynx and hypopharynx, a higher number of complications may be expected. We prospectively evaluated the frequency and characteristics of intraoperative and postoperative complications of early and advanced tumors of the larynx and hypopharynx treated with CO2 laser surgery and the potential influence of the surgical learning curve on the complication rate.Methods.Two hundred seventy‐five patients operated in a tertiary referral center. Complications were classified either as major, requiring intensive medical treatment, blood transfusion, surgery, or ICU admission, or minor, resolving spontaneously or with conventional ambulatory treatment without sequelae. The surgical learning curve was analyzed by dividing the patients into two groups according to the date of surgery and then comparing the number of complications.Results.Complications occurred in 18.9% of patients; 9.8% were considered major and 9.1% minor. Complications included local infection (0.7%), emphysema (1%), cutaneous fistula (0.3%), postoperative bleeding (8%), airway ignition (0.3%), dyspnea (because of edema or stenosis) (1.8%), and swallowing difficulties or aspiration pneumonia (6.1%). The complication rate correlated significantly with tumor extension (p < .0001), the presence of diabetes mellitus (p = .01), and less surgical experience (p < .0001). Complications with severe sequelae occurred in two patients (p = .7).Conclusions.Complications after transoral laser surgery of larynx and hypopharynx carcinomas are relatively frequent (18.9%), but serious sequelae and mortality rate are low. Complications are associated with tumor extension, limited surgical experience, and diabetes mellitus. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Diagnostic delays in laryngeal carcinoma: Professional diagnostic delay is a strong independent predictor of survival
Authors: Teppo Heikki , Koivunen Petri , Hyrynkangas Kalevi , Alho Olli‐Pekka 
Published: April 2003

AbstractBackground.Clinical stage at the time of diagnosis is the most important determinant of prognosis in cancers of the head and neck. Accordingly, delay in diagnosis could worsen survival in laryngeal cancer, although this hypothesis has not been verified in previous studies.Methods.To determine the effects of patient and professional diagnostic delays on survival in patients with laryngeal squamous cell carcinoma (LSCC), a population‐based sample of 66 patients with LSCC in Northern Finland between 1990 and 1995 was investigated. In addition to clinical data from tertiary care units and mortality data from the national death register, we collected data about the first medical visit in primary care that resulted, subsequently, in the diagnosis of malignancy.Results.Long professional delay in diagnosis (≥12 months) was an independent and statistically significant determinant of worsened prognosis (adjusted relative hazard of death 4.74, p = .05). There was no correlation between patient delay and prognosis. Another significant factor related to impaired prognosis was advanced stage (IV vs I–III, adjusted relative hazard of death 5.18, p = .02). Long professional delay was not significantly related to any of the demographic or clinical characteristics.Conclusions.A long professional delay is a marked and independent determinant of impaired survival in laryngeal carcinoma and equals the effect of advanced stage. However, unlike in most other cancers, early symptoms and slow tumor growth give the physician a fairly long time to reach the correct diagnosis before the delay turns out to be fatal. © 2003 Wiley Periodicals, Inc. Head Neck 25:000–000, 2003
Significance of the juxtaoral organ (of Chievitz)
Authors: Pantanowitz Liron , Balogh Karoly 
Published: April 2003

AbstractBackground.Most physicians are unaware of the juxtaoral organ (of Chievitz) and its clinical significance. The aim of this review is to draw attention to the clinical importance of this organ.Methods.Review and interpretation of the English and non‐English literature pertaining to the juxtaoral organ.Results.The juxtaoral organ is a small structure located within the soft tissue overlying the angle of the mandible in the buccotemporal space. It is composed of an epithelial parenchyma embedded in a highly organized connective tissue stroma rich in nerves and sensory receptors innervated by the buccal nerve. This metabolically active structure presumably serves as a mechanosensor in the lateral wall of the oral cavity. Needless surgical removal of this juxtaoral structure is therefore best avoided. In children, the normal organ may be discovered as a small mass in the cheeks, which may lead to extensive and unnecessary investigations. Hyperplasia of the parenchyma may occur, but carcinoma originating from this organ has not been reported.Conclusion.Awareness of this normal anatomic structure is important, because the finding of epithelial islands intimately admixed with nerves could be misinterpreted as perineural invasion by carcinoma. © 2002 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003