BRCA2 mutation in a family with hereditary prostate cancer

Grönberg, Henrik; Åhman, Anna‐Karin; Emanuelsson, Monica; Bergh, Anders; Damber, Jan‐Erik; Borg, Åke

doi:10.1002/1098-2264(2000)9999:9999<::aid-gcc1090>3.0.co;2-u

Cited by 27 publications

(16 citation statements)

References 13 publications

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“…26 LOH was also studied in four prostate tumours and one breast tumour from the previously mentioned Swedish family; two of the prostate tumours demonstrated LOH at BRCA2 . 34 Similarly, in our French Canadian family, LOH was observed in one of two prostate tumours from BRCA2 carriers.…”

Section: Diagnosissupporting

confidence: 60%

“…31, 32 The Ashkenazi Jewish BRCA2 founder mutation, c.5946delT (p.Ser1982fs), co0nfers a threefold increased risk for prostate cancer, and carriers are more likely to develop high-grade prostate cancer than noncarriers. 33 In the large Swedish family reported by Gronberg et al , 34 a truncating BRCA2 mutation (c.5823delA [p.Val1942fs]) was responsible for hereditary prostate cancer in the father and four of his sons who developed early-onset disease. This mutation was also detected in three daughters diagnosed with breast cancer.…”

Section: Diagnosismentioning

confidence: 99%

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Familial prostate cancer: the damage done and lessons learnt

et al. 2013

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Background A 51-year-old French Canadian man commenced screening for prostate cancer at the request of his family physician given his extensive family history of prostate cancer in five brothers, his father and two paternal uncles. His prostate specific antigen (PSA) level was 4.9ng/ml and a subsequent six-core biopsy revealed the presence of a prostate adenocarcinoma with a Gleason score of 7 (3+4). He was treated with a radical prostatectomy. Repeat PSA tests revealed a gradual rise in PSA levels despite androgen deprivation therapy with bicalutamide and goserelin over the course of 3 years. Genetic evaluation was undertaken in view of his personal and family history. The proband died a year later of widespread metastasis, at the age of 58. Investigations Doppler ultrasound for the proband’s leg, abdominal and pelvic computed tomography (CT) scan with intravenous (IV) and oral contrast as well as chest CT with IV contrast for the assessment of metastatic prostate cancer; genetic counselling and mutation analysis for French Canadian founder mutations in the BRCA1 and BRCA2 genes; mutations specific analysis of the mother’s formalin-fixed, paraffin-embedded (FFPE) breast tissue blocks; examination of loss of heterozygosity at the BRCA2 gene locus; immunohistochemistry to determine the expression of the ERG nuclear oncoprotein in prostate tumours; genotyping with eight selected risk-associated single nucleotide polymorphisms (SNPs); genetic testing for the G84E variant in the HOXB13 gene Diagnosis Early-onset and aggressive prostate cancer associated with a missense French Canadian BRCA2 founder mutation, c.5857G>T (p.Glu1953*). Management Radical prostatectomy, hormone therapy with bicalutamide and goserelin, palliative chemotherapy initially with docetaxel plus prednisone then with mitoxantrone plus prednisone, as well as genetic counselling and testing for the proband and his family members.

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Section: Diagnosissupporting

confidence: 60%

Section: Diagnosismentioning

confidence: 99%

Familial prostate cancer: the damage done and lessons learnt

et al. 2013

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“…Similarly, there is sparse research investigating the clinical or pathological features associated with prostate cancer in male BRCA1 or BRCA2 mutation carriers. To date, only four studies have investigated this relationship [12][13][14][15]. The majority of studies suggest an association of BRCA1 or BRCA2 mutations and an earlier age of diagnosis, poorly-differentiated tumors and a relatively poor prognosis [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

“…To date, only four studies have investigated this relationship [12][13][14][15]. The majority of studies suggest an association of BRCA1 or BRCA2 mutations and an earlier age of diagnosis, poorly-differentiated tumors and a relatively poor prognosis [12][13][14]. However, as these studies investigated men already diagnosed with prostate cancer, they do not allow us to evaluate the efficacy of current screening practices and management.…”

Section: Introductionmentioning

confidence: 99%

Male BRCA1 and BRCA2 mutation carriers: a pilot study investigating medical characteristics of patients participating in a prostate cancer prevention clinic

et al. 2005

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“…While the loss of BRCA2 function and its consequences in prostate cancer is being reconsidered [50], [51], [52], [53], BRCA2 is generally regarded as a “tumor suppressor”, with an established role in maintaining genomic stability via its function in the homologous recombination pathway for double-strand DNA repair. This result is supporting its proposed function.…”

Section: Resultsmentioning

confidence: 99%

Cancer Biomarker Discovery: The Entropic Hallmark

Berretta

Moscato

2010

PLoS ONE

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BackgroundIt is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods.Methodology/Principal FindingsUsing melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer.Conclusions/SignificanceWe thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.

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BRCA2 mutation in a family with hereditary prostate cancer

Cited by 27 publications

References 13 publications

Familial prostate cancer: the damage done and lessons learnt

Familial prostate cancer: the damage done and lessons learnt

Male BRCA1 and BRCA2 mutation carriers: a pilot study investigating medical characteristics of patients participating in a prostate cancer prevention clinic

Cancer Biomarker Discovery: The Entropic Hallmark

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