A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

Friend, Stephen H.; Bernards, René; Rogelj, Snezna; Weinberg, Robert A.; Rapaport, Joyce M.; Albert, Daniel M.; Dryja, Thaddeus P.

doi:10.1038/323643a0

Cited by 2,667 publications

(1,136 citation statements)

References 36 publications

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“…Therefore, loss or alteration of p16INK4 expression would affect the functions of p110 RB . Thus, it seems that loss of p16INK4 and loss of RB may have similar effects on cell cycle progression and that they are part of the same pathway in tumorigenesis; this has a special meaning in bone sarcomas, in which RB1 mutations have been demonstrated to happen non-randomly [2,3].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the p16INK4 and TP53 tumor suppressor genes in bone sarcoma pediatric patients

Patiño-García

Sierrasesúmaga

1997

Cancer Genetics and Cytogenetics

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Recent data suggest that deletion of p16INK4 and mutation of TP53 are among the most common genetic events in the development of human cancer, since the codified proteins act as brakes of the abnormal cell cycle. As the molecular events leading to the development of pediatric bone sarcomas remain unclear, we analyzed 75 osteosarcoma and Ewing sarcoma samples from 43 pediatric patients to search for alterations at the TP53 or p16INK4 tumor suppressor genes. By means of PCRDGGE (polymerase chain reaction and denaturing gradient gel electrophoresis) we detected TP53 point mutations in 18.6% of the tumor samples, but no constitutional mutations. In the analysis of p16INK4, 7% of the samples harbored deletions of the gene but no point mutations were detected by SSCP (single strand conformation polymorphism) analysis, just the polymorphism Ala -› Thr at codon 148. These data support the hypothesis that TP53 alterations may play a role in the development of pediatric bone tumors and that the primary mechanism of inactivation of p16INK4 seems to be homozygous deletion rather than point mutation.

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Section: Discussionmentioning

confidence: 99%

Analysis of the p16INK4 and TP53 tumor suppressor genes in bone sarcoma pediatric patients

Patiño-García

Sierrasesúmaga

1997

Cancer Genetics and Cytogenetics

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“…In 1971, the existence of the RB gene was initially postulated on the basis of the incidence of retinoblastoma in children (Knudson, 1971), and in 1986, its cDNA was cloned (Friend et al, 1986) and, almost independently, other investigators recognized a set of cellular factors initially identified for their ability to physically interact with the Adenovirus 5 E1A oncoprotein. Indeed, major bands representing these proteins were named after their apparent SDS-PAGE molecular mass (Harlow et al, 1986), that is, p60, p105, p107, p130 and p300.…”

Section: And References Therein)mentioning

confidence: 99%

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Mileo²,

2006

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“…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).…”

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confidence: 99%

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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A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

Cited by 2,667 publications

References 36 publications

Analysis of the p16INK4 and TP53 tumor suppressor genes in bone sarcoma pediatric patients

Analysis of the p16INK4 and TP53 tumor suppressor genes in bone sarcoma pediatric patients

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

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

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