The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas View Full Text


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Article Info

DATE

2008-09-09

AUTHORS

Jason I Herschkowitz, Xiaping He, Cheng Fan, Charles M Perou

ABSTRACT

IntroductionBreast cancers can be classified using whole genome expression into distinct subtypes that show differences in prognosis. One of these groups, the basal-like subtype, is poorly differentiated, highly metastatic, genomically unstable, and contains specific genetic alterations such as the loss of tumour protein 53 (TP53). The loss of the retinoblastoma tumour suppressor encoded by the RB1 locus is a well-characterised occurrence in many tumour types; however, its role in breast cancer is less clear with many reports demonstrating a loss of heterozygosity that does not correlate with a loss of RB1 protein expression.MethodsWe used gene expression analysis for tumour subtyping and polymorphic markers located at the RB1 locus to assess the frequency of loss of heterozygosity in 88 primary human breast carcinomas and their normal tissue genomic DNA samples.ResultsRB1 loss of heterozygosity was observed at an overall frequency of 39%, with a high frequency in basal-like (72%) and luminal B (62%) tumours. These tumours also concurrently showed low expression of RB1 mRNA. p16INK4a was highly expressed in basal-like tumours, presumably due to a previously reported feedback loop caused by RB1 loss. An RB1 loss of heterozygosity signature was developed and shown to be highly prognostic, and was potentially a predictive marker of response to neoadjuvant chemotherapy.ConclusionsThese results suggest that the functional loss of RB1 is common in basal-like tumours, which may play a key role in dictating their aggressive biology and unique therapeutic responses. More... »

PAGES

r75

References to SciGraph publications

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    http://scigraph.springernature.com/pub.10.1186/bcr2142

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    43 schema:description IntroductionBreast cancers can be classified using whole genome expression into distinct subtypes that show differences in prognosis. One of these groups, the basal-like subtype, is poorly differentiated, highly metastatic, genomically unstable, and contains specific genetic alterations such as the loss of tumour protein 53 (TP53). The loss of the retinoblastoma tumour suppressor encoded by the RB1 locus is a well-characterised occurrence in many tumour types; however, its role in breast cancer is less clear with many reports demonstrating a loss of heterozygosity that does not correlate with a loss of RB1 protein expression.MethodsWe used gene expression analysis for tumour subtyping and polymorphic markers located at the RB1 locus to assess the frequency of loss of heterozygosity in 88 primary human breast carcinomas and their normal tissue genomic DNA samples.ResultsRB1 loss of heterozygosity was observed at an overall frequency of 39%, with a high frequency in basal-like (72%) and luminal B (62%) tumours. These tumours also concurrently showed low expression of RB1 mRNA. p16INK4a was highly expressed in basal-like tumours, presumably due to a previously reported feedback loop caused by RB1 loss. An RB1 loss of heterozygosity signature was developed and shown to be highly prognostic, and was potentially a predictive marker of response to neoadjuvant chemotherapy.ConclusionsThese results suggest that the functional loss of RB1 is common in basal-like tumours, which may play a key role in dictating their aggressive biology and unique therapeutic responses.
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    51 ConclusionsThese results
    52 DNA samples
    53 IntroductionBreast cancer
    54 MethodsWe
    55 RB1 locus
    56 RB1 loss
    57 RB1 mRNA
    58 RB1 protein expression
    59 Rb1
    60 aggressive biology
    61 alterations
    62 analysis
    63 basal-like subtype
    64 basal-like tumors
    65 biology
    66 breast cancer
    67 breast carcinoma
    68 cancer
    69 carcinoma
    70 chemotherapy
    71 common event
    72 differences
    73 distinct subtypes
    74 events
    75 expression
    76 expression analysis
    77 feedback loop
    78 frequency
    79 frequency of loss
    80 functional loss
    81 gene expression analysis
    82 genetic alterations
    83 genome expression
    84 genomic DNA samples
    85 group
    86 heterozygosity
    87 high frequency
    88 human breast carcinoma
    89 key role
    90 loci
    91 loop
    92 loss
    93 loss of heterozygosity
    94 low expression
    95 luminal B tumors
    96 mRNA
    97 markers
    98 neoadjuvant chemotherapy
    99 occurrence
    100 overall frequency
    101 p16INK4a
    102 polymorphic markers
    103 predictive marker
    104 primary human breast carcinomas
    105 prognosis
    106 protein 53
    107 protein expression
    108 report
    109 response
    110 results
    111 retinoblastoma tumor suppressor
    112 role
    113 samples
    114 signatures
    115 specific genetic alterations
    116 subtypes
    117 subtyping
    118 suppressor
    119 therapeutic response
    120 tumor protein 53
    121 tumor subtyping
    122 tumor suppressor
    123 tumor types
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