bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of heterozygosity in sporadic primary cutaneous melanoma
Authors: Healy Eugene , Rehman Ishtiaq , Angus Brian , Rees Jonathan L. 
Published: February 2007

AbstractDifficulties in obtaining clinical samples from primary melanomas have meant that most genetic analyses of melanoma have concentrated on cell lines and metastases. Because the Breslow thickness of the primary tumour is the single best prognostic indicator, it is important to identify genetic abnormalities in primary melanomas and relate these changes to the thickness of the lesion. We have investigated 47 sporadic melanomas, of which 41 were primary lesions, for loss of heterozygosity (LOH) on several chromosomal arms, including areas where genes involved in familial melanoma and other relevant hereditary syndromes map, and where LOH has previously been reported in cell lines or metastatic lesions. LOH was identified at 66 (18%) of 358 informative loci in primary melanomas, and there was a significant relationship between the overall frequency of LOH and Breslow thickness (P < 0.0005). Loss of chromosome arm 9p was most frequent, occurring in 15 (47%) of 32 informative primary tumours, and was observed in 3 of 11 informative lesions ≦ 1.5 mm in depth. LOH on chromosome arms 3p, 6q, 10q, 11q, and 17p was also relatively frequent, with loss of 3p and 10q heterozygosity in lesions ≦ 1.5 mm in depth, while LOH on 6q, 11q, and 17p was only detected in more invasive tumours. The results suggest that loss of these chromosome regions are important in sporadic cutaneous melanoma, and are consistent with chromosome arm 9p loss occurring before loss of other chromosome arms.
Defining the position of the breakpoint of the constitutional t(3;6) occurring in a family with renal cell carcinoma
Authors: van den Berg Anke , van der Veen Anneke Y. , Hulsbeek Miriam M. F. , Kovacs Gyula , Gemmill Robert M. , Drabkin Harry A. , Buys Charles H. C. M. 
Published: February 2007

AbstractIn a family with a constitutional translocation t(3;6), the oldest member carrying the translocation had developed multiple nonpapillary renal cell carcinomas (RCCs). The translocation breakpoint was positioned between 3p13 and 3p14.1. This is close to the region in which a t(3;8) breakpoint has been reported in a family with hereditary RCC. We defined the location of the t(3;6) and t(3;8) breakpoints by fluorescence in situ hybridization (FISH) analysis with yeast artificial chromosomes (YACs) from the 3p14–13 region. Both interphase nuclei and metaphase cells from translocation‐carrying members of both families have been used, allowing the definition of flanking YACs for each breakpoint. We could thereby clearly confirm that the breakpoints are different, the t(3;8) breakpoint being most distal. In addition, we have shown that both translocation breakpoints are located distal to the homozygously deleted region in the U2020 lung cancer cell line.
Region‐specific loss of heterozygosity on chromosome 19 is related to the morphologic type of human glioma
Authors: Ritland Steven R. , Ganju Vinod , Jenkins Dr.Robert B. 
Published: February 2007

AbstractAllelic mutation on chromosome 19 has previously been reported as a frequent genetic event in human glial tumors. In an effort to localize specific regions of importance on this chromosome better, 13 highly polymorphic genetic markers distributed along the length of chromosome 19 were used for evaluation of loss of heterozygosity (LOH) and microsatellite instability in a total of 100 brain tumors, including 75 astrocytomas (55 grade 4; 7 grade 3; 5 grade 2; 6 grade 1; and 2 other), 17 oligodendrogliomas (1 grade 4; 5 grade 3; 10 grade 2; and 1 grade 1), and 8 mixed oligoastrocytomas (MOA) (3 grade 4; 2 grade 3; and 3 grade 2). No microsatellite expansion was observed in these glial tumors for any of the chromosome 19 loci examined. LOH for loci on chromosome 19 was detected in 23/74 informative astrocytomas (31%), 11/17 oligodendrogliomas (65%), and 3/8 MOA (38%). Partial deletion of chromosome 19 occurred more frequently (31/37 cases) than did loss of one whole copy of the chromosome, and a morphology‐specific pattern of LOH was observed. In 12/14 (86%) instances of chromosome 19 deletion in oligodendrogliomas and MOA, the 19q arm showed LOH, whereas the 19p arm showed no loss for all informative loci. Conversely, in 17/23 (74%) instances of chromosome 19 deletion in astrocytomas, the 19p arm showed LOH, whereas the 19q arm showed no loss for one or more loci. Thus, loss of 19q and retention of 19p are strongly associated with oligodendroglioma and MOA, whereas loss of 19p and retention of distal 19q is associated with astrocytoma. These data indicate that two or more tumor suppressor genes may reside on chromosome 19, one on 19p important in the development of astrocytomas, and one on 19q important in oligodendrogliomas and MOA.
Localization of the 8;13 translocation breakpoint associated with myeloproliferative disease to a 1.5 mbp region of chromosome 13
Authors: Kempski Helena , Macdonald Donald , Michalski Antony J. , Roberts Terry , Goldman John M. , Cross Nicholas C. P. , Cowell Dr.John K. 
Published: February 2007

AbstractThere are five reported cases of an atypical myeloproliferative disorder in which the leukemia cells have a consistent t(8;13)(p11;q12) translocation. We analyzed the breakpoint in metaphases from two of these patients by fluorescence in situ hybridization using a series of yeast artificial chromosomes (YACs) derived from the 13q12 region. We found that a YAC containing the FLT1 and FLT3 oncogenes was localized distal to the 13q12 breakpoint and was not rearranged. YAC 66, a YAC that lies immediately adjacent to the chromosome 13 centromere, was localized proximal to the 13q12 breakpoint and was not rearranged. A third YAC, which is located between FLT1 and YAC 66, was unrearranged in normal metaphase chromosomes, but showed hybridization signals on both derivative chromosomes in both cases. Thus, the breakpoints in these two cases are localized to the same 1.5 Mbp region of 13q12. This may be the site of an unidentified gene involved in the pathogenesis of some types of leukemia.
Allelic losses in human chromosome II in lung cancers
Authors: Lizuka Masayoshi , Sugiyama Yuki , Shiraishi Masahiko , Jones Carol , Sekiya Takao 
Published: February 2007

AbstractThe relatively frequent loss of heterozygosity at loci on the short arm of chromosome 11 in human lung cancers has suggested the presence of a putative tumor suppressor gene. For location of the gene, a fine deletion map of human chromosome 11 was constructed by analysis of DNAs from 79 lung cancers with 31 sequence‐tagged‐site markers that dotted chromosome 11 and detected polymorphic changes in nucleotide sequences. The results showed that three regions, 11p 12‐p 15, 11q12, and 11 q14‐q24, were commonly deleted in a considerable number of cancers, indicating the possible presence of more than one tumor suppressor gene. The range of deletion in the 11p15 region was estimated to be 4.5 megabases. That in the 11q24‐q24 region was divided into two portions: one was 3 cM in length, and the other was longer and could not be specified because of lack of appropriate markers. The deletion in the 11q12 region was so short that two markers flanking the region could not be identified by genetic analysis. © 1995 Wiley‐Liss, Inc.
Genetic mosaicism at the insulin locus in liver associated with childhood hepatoblastoma
Authors: Simms Lisa A. , Reeve Anthony E. , Smith Peter J. 
Published: February 2007

AbstractHepatoblastoma is commonly associated with loss of heterozygosity (LOH) involving chromosome region IIp 15.5. This region may contain an as yet unidentified tumor suppressor gene relevant to this and other tumors associated with the Beckwith Wiedemann syndrome. Using the insulin (INS) locus as a marker for this region we have identified two of three patients with hepatoblastoma whose livers demonstrated genetic mosaicism. One tumor arose from the clone demonstrating LOH in the liver while the other arose from the clone without LOH. © 1995 Wiley‐Liss, Inc.
Detection of multiple gains and losses of genetic material in ten glioma cell lines by comparative genomic hybridization
Authors: Mohapatra Gayatry , Kim Dong H. , Feuerstein Burt G. 
Published: February 2007

AbstractA protocol for comparative genomic hybridization by use of nucleotides directly labeled with fluorochromes was used to map regions of deletion and amplification in ten glioma cell lines. The protocol greatly reduced experimental artifacts. We detected several genetic aberrations, including whole chromosome loss and gain, partial loss and gain, possible isochromosome, and higher level DNA amplification. The most frequent losses (in order of frequency) occurred on chromosomes 10, 18, 13, 11, 9, 14, 4, 6, 1, and X. The most common gain occurred on chromosome 7. Several sites of previously known and unknown amplifications were observed. © 1995 Wiley‐Liss, Inc.
Homozygous Deletions and Loss of Expression of the CDKN2 gene occur frequently in head and neck squamous cell carcinoma cell lines but infrequently in primary tumors
Authors: Lydiatt William M. , Murty V. V. V. S. , Davidson Bruce J. , Xu Li , Dyomina Katerina , Sacks Peter G. , Schantz Stimson P. , Chaganti R. S. K. 
Published: February 2007

AbstractDeletion of 9p21–22 is a common genetic alteration in dysplastic, in situ, and invasive head and neck squamous cell carcinoma (HNSCC). However, a candidate tumor suppressor gene (TSG) at this site has thus far not been identified in HNSCC. We report homozygous deletion of the recently identified multiple tumor suppressor I (MTSI)/cyclin‐dependent kinase‐4‐inhibitor (CDKN2) gene mapped to 9p21, which encodes the p16 protein, a regulator of cyclin‐dependent kinase 4, in six of 16 HNSCC cell lines. We also show absence of the CDKN2 mRNA in all cell lines with CDKN2 deletion as well as in an additional two cell lines without deletion. Overall, we have identified 9p abnormalities in 12 of 16 (75%) cell lines, at least nine of which involved CDKN2. We further demonstrate that the CDKN2 deletion in HNSCC is located within a previously described region of allelic loss between D9S171 and IFNW, which spans a 4 cM region of 9p. However, examination of 36 primary tumors revealed genetic alterations in only seven of 36 (19%) tumors. These results suggest that genetic alterations at CDKN2 are frequent in HNSCC cell lines, but the role of this gene in primary tumors is less compelling. CDKN2 does not appear to be the only TSG on 9p21 in HNSCC, and our results suggest that another region of deletion exists proximal to the IFNW locus. © 1995 Wiley‐Liss, Inc.
Childhood acute lymphoblastic leukemia with equivocal chromosome markers of the t(I;I9) translocation
Authors: Filatov Leonid V. , Behm Frederick G. , Pui Ching‐Hon , Head David R. , Downing James R. , Raimondi Susana C. 
Published: February 2007

AbstractThe t(1;19)(q23;p13) or its derivative encodes an E2A‐PBX1 fusion transcript and protein that has been shown to have important prognostic and therapeutic implications in patients with acute lymphoblastic leukemia (ALL). We describe two childhood cases in which a der(22)t( 1;22)(q21‐23;p13) cytogenetically mimicked a der( 19)t( 1; 19)(q23;p 13). In one case, which was phenotyped as early pre‐B ALL with hyperdiploidy but lacked evidence of an E2A‐PBX1 gene fusion by molecular study, the poor banding quality of chromosomes led to misinterpretation of the cytogenetic findings; a correct diagnosis was established only after analysis by the fluorescence in situ hybridization (FISH) method. The second case, which was classified as pseudodiploid pre‐B ALL, had both a derivative 19 and a derivative 22 but lacked sufficient cells for evaluation of E2A‐PBX1 gene fusion. This case was included in order to compare the der(19)t(1;19) and the der(22)t(1;22) and to pinpoint the difficulty in distinguishing these markers. FISH analysis can resolve diagnostic uncertainty in cases of ALL with equivocal chromosome 19 markers. © 1995 Wiley‐Liss, Inc.
Monochromosome transfers to syrian hamster BHK cells via microcell fusion provide functional evidence for suppressor genes on human chromosome 9 both for anchorage independence and for tumorigenicity
Authors: Islam M. Quamrul , Islam Khaleda , Levan GÖRan , Horvath György 
Published: February 2007

AbstractWe previously identified an anchorage independence‐suppressor gene, SAII, on rat chromosome (RNO) 5. RNO5 is homologous to human chromosomes (HSA) I and 9. In order to find the human homolog of the SAII gene, we transferred HSAI and HSA9 to an anchorage‐independent and tumorigenic Syrian hamster BHK 191‐5C cell line by microcell fusion. For HSA9, we used a t(X; 9)‐derivative chromosome to force the retention of this chromosome in hybrids by hypoxanthine‐aminopterin‐thymidine (HAT) selection. To study the possible effect of the X portion of the der(9)t(X; 9), we also transferred a normal X to 191‐5C cells. For HSAI, a neo‐tagged chromosome was introduced. Following the transfer of der(9)t(X; 9) to 191 ‐5C cells, the hybrid cells became anchorage dependent and nontumorigenic, and, upon the loss of this chromosome, the cells regained their tumorigenic and anchorage‐independent phenotypes. The transfer of HSAX or HSAI, on the other hand, affected neither of these phenotypes. These results provide functional proof of suppressor genes on HSA9 involving both anchorage independence and tumorigenicity. In addition, our data suggest the presence of another gene on HSA9 that causes a negative growth effect and whose phenotypic expression, contrary to the suppressor genes, is dosage dependent. © 1995 Wiley‐Liss, Inc.
Cytogenetic findings in 31 papillary thyroid carcinomas
Authors: Roque Lúcia , Clode Ana L. , Gomes Paula , Rosa‐Santos Jorge , Soares Jorge , Castedo Sérgio 
Published: February 2007

AbstractChromosome studies performed on 3I papillary thyroid carcinomas (PTCs) revealed clonal numerical and structural abnormalities in I2 tumors. The numerical clonal aberrations found were trisomy 2, trisomy 7, and loss of the Y chromosome. A nonrandom telomeric association, tas( I5; I6)(p I3; p I3), was observed in one carcinoma. Structural alterations with a breakpoint at I0q II.2 were detected in two tumors. Other chromosomes involved in rearrangements were chromosomes I, 2, 3, 5, 7, 9, II, 12, and 14. The observation of clonal changes of chromosome 2 [i(2)(qI0) and trisomy 2] in two tumors, which were both histologically classified as tall‐cell PTC variants, suggests that gain of 2q may be important in the development of this morphological variant. © 1995 Wiley‐Liss, Inc.
Loss of heterozygosity from the short arm of chromosome 8 is an early event in breast cancers
Authors: Yarernko M. Lisa , Recant Wendy M. , Westbrook Carol A. 
Published: February 2007

AbstractLoss of heterozygosity (LOH) from the short arm of chromosome 8 (8p) is common to many human carcinomas, including those of the colon and prostate. It localizes to two discrete regions, 8p21 and 8p22. This suggests the presence of at least two tumor suppressor genes (TSGs) on this chromosome arm. Human breast cancers show consistent 8p deletions in cytogenetic studies, chromosome 8 aneusomy and isochromosome 8q, indicating that the relevant gene(s) may play a role, but the results of molecular analyses of chromosome 8 in breast cancer have been variable. We present here data for 8p LOH in an unselected series of human breast cancers with the use of three CA‐repeat markers that showed high rates of LOH in other tumors. All cases were informative for at least one marker, and LOH was seen in 11 of 20 cases (55%). LOH was more frequent for the 8p22 markers D8S254 and D8S 133 than for NEFL in 8p21. Regional metastases of the tumors showed allele profiles identical to those of their primaries regardless of whether there was LOH or retention of alleles. One case of microsatellite instability (RER+) was seen. LOH did not correlate with receptor status, ploidy, percentage of cells in S phase, or tumor size: We observed LOH at equal rates in small (<2 cm) and in larger (>2 cm) tumors. The data suggest that LOH from 8p is frequent in human breast cancers and that loss of the putative 8p TSG may be an important event in early stage breast cancer. © 1995 Wiley‐Liss, Inc.
Isochromosome 17q demonstrated by interphase fluorescence in situ hybridization in primitive neuroectodermal tumors of the central nervous system
Authors: Biegel Jaclyn A. , Rorke Lucy B. , Janss Anna J. , Sutton Leslie N. , Parmiter Annette H. 
Published: February 2007

AbstractWe previously reported an i(17q) as a non‐random finding in childhood primitive neuroectodermal tumors (PNETs) of the central nervous system. In the present study, we describe a two‐color interphase fluorescence in situ hybridization (FISH) assay for detection of chromosome 17 abnormalities in tumors. Thirty‐four PNETs were analyzed by FISH with a series of chromosome 17‐specific probes which map to 17p13.3‐17q25. The results from the FISH assay were then compared to the karyotypes prepared from the tumors. Ten of the 34 cases demonstrated an i(17q) by FISH and standard cytogenetics. Two PNETs were shown to have an i(17q) by FISH alone, and three additional tumors had deletions of 17p. Thus, a total of 15 of 34 (44%) of the PNETs in this series had a deletion of 17p. This study confirms and extends our previous reports that an i(17q) is the most common cytogenetic abnormality in PNETs. The interphase FISH assay which we employed will have clinical utility for diagnosis of children with malignant brain tumors, and it may be used for identification of tumors with 17p deletions for molecular studies aimed at identifying disease genes.
No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis
Authors: van Echten Jannie , Oosterhuis J. Wolter , Looijenga Leendert H. J. , van de Pol Mirjam , Wiersema Janneke , Meerman Gerard J. Te , Koops Heimen Schraffordt , Sleijfer Dirk Th. , Jong Bauke De 
Published: February 2007

AbstractMalignant transformation may be caused by gene deregulation resulting from specific chromosomal rearrangements, by amplification, by mutations in proto‐oncogenes, by loss of tumor suppressor genes, or a combination of these. We investigated the role of numerical and structural chromosomal abnormalities in 102 cytogenetically abnormal cases of primary testicular germ cell tumors of adolescents and adults (TGCT) [32 seminomas (SE) and 70 nonseminomatous germ cell tumors (NS)]. We confirmed that an isochromosome for 12p, i(12p), is the only consistent structural chromosomal abnormality in TGCT, present in about 70% of our cases. Both the frequency and the number of copies of i(12p) are higher in NS than in SE. This may suggest that i(12p) is involved in tumor progression. Besides i(12p), several clonal structural chromosomal abnormalities were found, but none appeared to be specific. SE and NS had chromosome numbers in the triploid range, with significantly higher numbers in SE than in NS (average modal chromosome number of 73.4 in SE and 65.0 in NS). Both in SE and NS, some chromosomes were significantly underrepresented (e.g., 11, 13, 18, and Y) and others overrepresented (e.g., 7, 8, 12, 21, and X). In SE, a significantly higher copy number of chromosomes 7, 15, 19, and 22 was found and a significantly lower number of chromosome 17, compared with NS. These chromosomes may play an important role in the differentiation of TGCT.
Predominance of normal karyotype in colorectal tumors from hereditary non‐polyposis colorectal cancer patients
Authors: Muleris Martine , Dutrillaux Anne Marie , Olschwang Sylviane , Salmon Remy Jacques , Dutrillaux Bernard 
Published: February 2007

AbstractWe report the cytogenetic study of 9 colorectal tumors arising in patients with hereditary non‐polyposis colorectal cancer (HNPCC). According to the cytogenetic classification of colorectal tumors previously proposed by us, 2 cases were of the trisomic type, 2 were of the monosomic type, and 5 had a normal karyotype. This represents a significant excess of tumors with normal karyotype in HNPCC tumors (56%) compared to sporadic cases (10/184 = 5%).
Genetic alterations in breast cancer
Authors: Bièche Ivan , Lidereau Rosette 
Published: February 2007

AbstractThe etiology of breast cancer involves a complex interplay of various factors, including genetic alterations. Many studies have been devoted to the identification and characterization of mutations that occur frequently during breast tumorigenesis. The major types of genetic abnormalities that are frequently observed in breast tumors are amplification of protooncogenes (MYC, ERBB2) and DNA from chromosome band 11q13; mutation of TP53; and loss of heterozygosity from chromosomes and chromosome arms 1, 3p, 6q, 7q, 8p, 11, 13q, 16q, 17, 18q, and 22q. The latter may correspond to losses or inactivations of tumor suppressor genes. Recently, linkage analyses of large families with a predisposition to breast cancer have been performed in order to map breast cancer susceptibility genes (TP53, BRCA1, BRCA2). The findings have thrown light on the molecular mechanisms of breast cancer and have enabled various genetic markers to be used in clinical oncology.
Mapping of chromosomal gains and losses in prostate cancer by comparative genomic hybridization
Authors: Joos Stefan , Bergerheim Ulf S. R. , Pan Yi , Matsuyama Hideyasu , Bentz Martin , Manoir Stanislas Du , Lichter Peter 
Published: February 2007

AbstractComparative genomic hybridization (CGH) allows detection of chromosomal imbalances in whole genomes in a comprehensive manner. With this approach, ten cases of prostate cancer (seven primary tumors and three metastases) were analyzed. Frequent chromosomal gains detected by CGH involved chromosome arms 7q, 8q, 9q, and 16p, and chromosomes 20 and 22, as well as frequent losses of chromosome arms 16q and 18q, in at least three of the ten cases. Overrepresentation of chromosome arm 9q has not been described in published reports. The CGH data were compared with results of a loss of heterozygosity (LOH) study, in which complete allelotyping was performed in the same prostate tumors with 74 different polymorphic markers. In general, a high concordance between the CGH and LOH results was observed (92%). Tumors revealing discrepancies by CGH and LOH analysis were investigated further by interphase cytogenetics, and the resulting picture regarding the genomic alterations is discussed in detail.