Cloning and Gene Mapping of the Chromosome 13q14 Region Deleted in Chronic Lymphocytic Leukemia

Kalachikov, Sergey; Migliazza, Anna; Cayanis, Eftìhia; Fracchiolla, Nicola; Bonaldo, Maria F.; Lawton, Lee N.; Jelenc, Pierre C.; Ye, X.; Qu, Xiaoyan; Chien, Minchen; Hauptschein, Robert; Gaïdano, Gianluca; Vitolo, Umberto; Saglio, Giuseppe; Resegotti, L; Brodjansky, V.; Yankovsky, N. K.; Zhang, P.; Soares, Marcelo B.; Russo, James J.; Edelman, Isidore S.; Efstratiadis, Argiris; Dalla‐Favera, Riccardo; Fischer, Stuart G.

doi:10.1006/geno.1997.4747

Cited by 121 publications

(105 citation statements)

References 27 publications

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“…Detailed deletion mapping by FISH with probes from this contig allowed us to narrow down a commonly deleted segment of 400 kb (PAC-272-3, PAC-272-1-1, PAC-3, PAC-1, PAC-58 and PAC-48). This deletion region corresponds well to a deletion region most recently reported by Kalachikov et al (1997). In this study some tumors showed discontinuous deletions, similar to the results obtained by Bullrich et al (1996).…”

Section: Discussionsupporting

confidence: 92%

“…In the PAC-272-3 region several exons were identi®ed which match to known ESTs and are contained in isolated cDNAs. Two of the identi®ed transcribed sequences correspond to ESTs recently reported by Kalachikov et al (1997). We identi®ed two additional cDNAs mapping to the smallest commonly a ected segment delineated by PAC-272-3 in our study which were transcribed in a variety of tissues.…”

Section: Discussionmentioning

confidence: 55%

“…Reverse-transcribed RNA from the tissues indicated and four B-CLL samples with monoallelic 13q14 deletions were used as templates High expression levels of a 1.5 kb transcript are found in spleen and small intestine whereas a weaker expression is detectable in other tissues critical region at the distal end of the 400 kb common deletion. This segment corresponds to the distal end of the critical region identi®ed by Kalachikov et al (1997), which was also a ected in two tumors with discontinuous deletions. A similar 13q14 deletion pattern as in B-CLL was observed in MCL.…”

Section: Discussionmentioning

confidence: 97%

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Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma

et al. 1998

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Deletions a ecting the interval between the RB1 gene and marker D13S25 at band 13q14 are the most frequent genetic abnormalities of B-cell chronic lymphocytic leukemia (B-CLL) and indicate the presence of a novel tumor suppressor gene in this region. In the current study, a high resolution physical map of fragments spanning one megabasepair (Mb) of genomic DNA at the critical 13q14 segment was constructed. To de®ne the minimal region of loss within the RB1 and D13S25 interval, we screened 322 B-CLLs for deletions at either of the two loci. Thirty mantle cell lymphomas (MCLs) were included in the analysis because we observed a 13q14 deletion pattern similar to B-CLL in this disease. The incidence of 13q14 deletions was 51% in B-CLL and 70% in MCL, respectively. No frequent loss of the BRCA2 gene at band 13q12 was found. Detailed deletion mapping at band 13q14 with probes from the RB1 ± D13S25 interval lead to the identi®cation of a critical deletion region 400 kb in size. Within this region two segments were most frequently a ected, one at D13S272 120 kb in size and another 240 kb distal of D13S272 80 kb in size. From these two segments expressed sequences were identi®ed as candidates for the putative 13q14 tumor suppressor gene involved in the pathogenesis of B-CLL and MCL.Keywords: deletion mapping; FISH; exon ampli®cation; DIRVISH The molecular pathogenesis of B-CLL, the most frequent leukemia in Western countries, is not well understood (Rozman and Montserrat, 1995). Although a number of recurrent chromosome aberrations have been identi®ed, no gene to date has been found to be consistently involved (Juliusson et al., 1990;DoÈ hner et al., 1997a).The most common structural chromosome aberrations in B-CLL involve band 13q14 (Juliusson et al., 1990), to which the RB1 tumor suppressor gene has been localized (Friend et al., 1986). Monoallelic RB1 deletion was frequently observed in B-CLL but disruption of both RB1 alleles occurred rarely (Liu et al., 1992(Liu et al., , 1993Stilgenbauer et al., 1993). Based on the observation that the distal marker D13S25 was deleted more frequently than RB1, a novel B-CLL tumor suppressor gene located in vicinity to this marker was postulated (Brown et al., 1993;Liu et al., 1993;Chapman et al., 1994).Subsequent studies aimed at the localization of this gene have been thus far inconclusive. Devilder et al.(1995) localized a minimal deletion segment distal of D13S25. However, comparing deletions of RB1 and D13S25 lead us to the hypothesis that the critical segment is localized proximal of D13S25 (Stilgenbauer et al., 1995). This was supported by Liu et al. (1995) who found loss of D13S319 located less than 680 kb proximal of D13S25 more frequently deleted than other 13q14 markers. Bullrich et al. (1996) recently assembled a YAC contig to order new markers in the region and identi®ed a minimal deletion between D13S25 and the marker 206XF12 located less than 550 kb proximal of D13S25. However, in this study deletions did not appear to cluster in a single critical region and the poten...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 97%

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Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma

et al. 1998

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“…5 Candidate genes in this region have been identified. 6 We have proposed the nearby BRCA2 gene at 13q12 as a tumour suppressor in CLL on the basis of fluorescent in situ hyridisation studies. 7 Mutations in TP53 and lesions indicating defective responses in DNA repair have been reported.…”

Section: Introductionmentioning

confidence: 99%

Anticipation in familial chronic lymphocytic leukaemia

Houlston

Catovsky

1998

Leukemia

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A recent analysis of literature reports of familial clusters of chronic lymphocytic leukaemia (CLL) suggested that affected offspring are diagnosed at an age 21 years less than CLL parents. Such an analysis risks sampling bias. We avoided these potential sources of bias by systematic ascertainment of CLL families. Statistical analysis of 10 such families showed a significant decline of 22 years between the mean ages at diagnosis of disease in parents and offspring. This confirms the analysis of literature reports and provides the first systematic investigation of a phenomenon which, if familial clustering of CLL cases is considered due to genetic effects, points to familial CLL manifesting anticipation.

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“…as the need arises in a given project. We provide three example projects, undertaken at Columbia, in which the IMP has been instrumental: (i) the generation of a high resolution YAC-cosmid map over most of the length of human chromosome 13 (Cayanis et al, 1998), (ii) the development of two highly annotated maps in the region surrounding BRCA2 (13q12.2; Fischer et al, 1996), and (iii) the CLL deletion locus (13q14.3; Kalachikov et al, 1997). This software developed on the UNIX platform is available by contacting the first author.…”

Section: Introductionmentioning

confidence: 99%

Integrated Mapping Package—A Physical Mapping Software Tool Kit

Zhang

Liao

et al. 1999

Genomics

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We have developed an integrated physical mapping computer software package (IMP), originally designed to support the physical mapping of human chromosome 13 and expanded to support several gene-identification projects based on the positional candidate approach. IMP displays map data in a form that provides useful guidelines to the end users. An integrated map with high resolution and confidence is constructed from different types of mapping data, including hybridization experiments, STS-based PCR assays, genetic linkage mapping, cDNA localization, and FISH data. The map is also designed to provide suggestions for specific experiments that are required to obtain maps with even higher resolution and confidence. To this end, the optimization employs multiple constraints that take into account already established STS "scaffold" maps. This software thus serves as an important general tool kit for physical mapping, sequencing, and gene-hunting projects.

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Cloning and Gene Mapping of the Chromosome 13q14 Region Deleted in Chronic Lymphocytic Leukemia

Cited by 121 publications

References 27 publications

Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma

Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma

Anticipation in familial chronic lymphocytic leukaemia

Integrated Mapping Package—A Physical Mapping Software Tool Kit

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