An unusually proximal deletion on the short arm of chromosome 3 in a patient with small cell lung cancer

Daly, Maria C.; Douglas, Jenny; Bleehen, Norman M.; Hastleton, P.; Twentyman, Peter R.; Sundaresan, Vasi; Carritt, B.; Bergh, Jonas; Rabbitts, Pamela

doi:10.1016/0888-7543(91)90227-6

Cited by 35 publications

(14 citation statements)

References 29 publications

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“…This represents a significant reduction in the previously defined minimally deleted region. Additional support for this conclusion came when the D3S3 locus was shown to be deleted in a LC tumor sample, whereas two other loci often involved in 3p deletions (D3F15S2 and D3S2) were shown to maintain two copies (26).…”

mentioning

confidence: 70%

See 1 more Smart Citation

Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21.

LaForgia

Morse

Levy

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

182

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mentioning

confidence: 70%

“…Cytogenetic reports suggest that the minimal deleted region is 3p14-23 in LC (10) and 3p14-pter in RCC (9). Two papers (22,26) reported progress in defining a smaller minimally deleted region in LC. Rabbitts et al (22) described a submicroscopic homozygous deletion involving the D3S3 locus in a LC cell line.…”

mentioning

confidence: 99%

Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21.

LaForgia

Morse

Levy

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

182

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“…We ®rst identi®ed loss of the chromosomal region 3p1474cen as important in lung tumours following a deletion mapping study of a primary carcinoma of the lung in which this region was heterozygously lost by interstitial deletion (Daly et al, 1991;Ganly et al, 1992). This was con®rmed by the detailed deletion mapping study of Hibi et al, 1992) which identi®ed three regions on 3p involved in lung tumour development of which 3p1474 centromere was one.…”

Section: Discussionmentioning

confidence: 99%

“…High resolution deletion mapping using VNTR probes has indicated three distinct regions involved in lung cancer development on this chromosome ± 3p25, 3p21.3 and 3p14 74cen (Hibi et al, 1992). We have concentrated on the most proximal of these three regions having described centromeric interstitial deletions in two primary small cell lung cancers (SCLC) (Daly et al, 1991;Ganly et al, 1992) and a homozygous deletion at 3p12-13 also in a SCLC sample (Rabbitts et al, 1990), the U2020 deletion. Further support for the importance of this region is provided by karyotype analyses in which deletions in proximal 3p are the only observable cytogenetic change.…”

Section: Introductionmentioning

confidence: 99%

Homozygous deletions at 3p12 in breast and lung cancer

et al. 1998

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We have constructed a physical map of the region homozygously deleted in the U2020 cell line at 3p12, including the location of putative CpG islands. Adjacent to one of these islands, we have identi®ed and cloned a new gene (DUTT1) and used probes from this gene to detect two other homozygous deletions occurring in lung and breast carcinomas: the smallest deletion is within the gene itself and would result in a truncated protein. The DUTT1 gene is a member of the neural cell adhesion molecule family, although its widespread expression suggests it plays a less specialized role compared to other members of the family.

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“…All DNA probes have been mapped to chromosome regions and have a known frequency for detecting reductions to allelic homozygosity in the examined tumor types (17)(18)(19)(20)(21)(22)(23). Each probe was isolated as an insert from the growth vector and labeled by the random priming procedure (24).…”

Section: Methodsmentioning

confidence: 99%

Distinct hypermethylation patterns occur at altered chromosome loci in human lung and colon cancer.

Makos

Nelkin

Lerman

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

140

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Regional increases in DNA methylation occur in normally unmethylated cytosine-rich areas in neoplastic cells. These changes could potentially alter chromatin structure to inactivate gene transcription or generate DNA instability. We now show that, in human lung and colon cancer DNA, hypermethylation of such a region consistently occurs on chromosome 17p in an area that is frequently reduced to homozygosity in both tumor types. Over the progression stages of colon neoplasia, this methylation change increases in extent and precedes the allelic losses on 17p that are characteristic of colon carcinomas. We also show on chromosome 3p that regional hypermethylation may nonrandomly accompany chromosome changes in human neoplasia. Increased methylation is consistent in small-cell lung carcinoma DNA at two 3p loci that are constantly reduced to homozygosity in this tumor, but it is not seen in colon cancer DNA, in which these loci are infrequently structurally altered.Alterations in DNA cytosine methylation are one of the most consistent, but poorly understood, molecular changes in human cancers (reviewed in refs. 1 and 2). These abnormalities appear early in progression of tumors and reflect an imbalance in the DNA methylation process that includes widespread hypomethylation (3), regional areas of hypermethylation (4), and an increased cellular capacity to methylate DNA (5, 6). The regional hypermethylation may be particularly important. Our laboratory (4) and others (7,8) have found this change in clusters of CpG dinucleotides near regulatory areas of genes. A normally unmethylated status of these "CpG islands" appears to be essential for active gene transcription (reviewed in ref. 9). Conversely, cytosine methylation within CpG islands can either stabilize or cause alterations in chromatin structure that render chromosome regions transcriptionally inactive (for review, ref. 10) or subject to DNA instability (11).We now explore whether chromosomal regions that are distinctively altered in human cancers are nonrandomly associated with hypermethylation and how the timing of this abnormality relates to changes in chromosome structure during tumor progression. A CpG-island-rich area on chromosome 17p, consistently reduced to homozygosity in both lung and colon cancers, is extensively hypermethylated in both tumor types. During progression stages for colon neoplasia, this abnormal methylation occurs early, increases in extent, and precedes allelic losses of the involved region. We also find that regions of chromosome 3p that are consistently reduced to homozygosity in lung, but not colon, cancers are hypermethylated only in lung cancer. We suggest that DNA hypermethylation nonrandomly marks chromosome regions altered during the development of specific tumors.

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An unusually proximal deletion on the short arm of chromosome 3 in a patient with small cell lung cancer

Cited by 35 publications

References 29 publications

Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21.

Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21.

Homozygous deletions at 3p12 in breast and lung cancer

Distinct hypermethylation patterns occur at altered chromosome loci in human lung and colon cancer.

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