Loss of heterozygosity atBRCA1/2 loci in hereditary and sporadic ovarian cancers

Brożek, Izabela; Ochman, Karolina; Dȩbniak, Jarosław; Morzuch, Lucyna; Ratajska, Magdalena; Stepnowska, Monika; Stukan, Maciej; Emerich, Janusz; Limon, Janusz

doi:10.1007/bf03195697

Cited by 10 publications

(9 citation statements)

References 17 publications

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“…LOH at chromosome 17 and chromosome arm 13q was recently described as a frequent phenomenon in hereditary as well as sporadic ovarian cancers (Brozek et al, 2009). In another study of 20 primary ovarian carcinomas, LOH at D17S855 was recorded with an incidence of 63%, which is quite similar to our findings (Hickey et al, 1999).…”

Section: Discussionsupporting

confidence: 88%

Loss of heterozygosity proximal to the M6P/IGF2R locus is predictive for the presence of disseminated tumor cells in the bone marrow of ovarian cancer patients before and after chemotherapy

Kuhlmann

Schwarzenbach

Otterbach

et al. 2011

Genes Chromosomes & Cancer

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Disseminated tumor cells (DTC) in the bone marrow (BM) are present in about 35% of ovarian cancers before surgery and after chemotherapy and are associated with worse prognosis. A molecular biomarker in the primary tumor predicting tumor cell spread would be highly desirable. The purpose of the study was to investigate loss of heterozygosity (LOH) in primary ovarian tumors at four ovarian cancer-relevant chromosomal loci involved in apoptosis, platinum sensitivity, or DNA-repair, to assess the prognostic value of LOH and to correlate LOH with DTC occurrence before surgery and after chemotherapy. Primary tumor DNA of 88 patients was analyzed for LOH at four polymorphic microsatellite markers using PCR-based fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. LOH at the entire marker set correlated with tumor grading (P = 0.0001) and histology (P = 0.004). LOH at marker D10S1765 correlated with FIGO stage (P = 0.046) and grading (P = 0.05), whereas LOH at D17S855 significantly associated with grading (P = 0.023) and histology (P = 0.012), respectively. DTC were detected in 49% of patients before surgery and in 50% of patients after chemotherapy. Interestingly, LOH proximal to D6S1581 significantly correlated with DTC presence before surgery (P = 0.05) and after chemotherapy (P = 0.022). Conclusively, our data suggest that allelic loss at D6S1581 (proximal to M6P/IGF2R locus) serves as a molecular biomarker for the presence of DTC in the BM before and after chemotherapy.

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Section: Discussionsupporting

confidence: 88%

Loss of heterozygosity proximal to the M6P/IGF2R locus is predictive for the presence of disseminated tumor cells in the bone marrow of ovarian cancer patients before and after chemotherapy

Kuhlmann

Schwarzenbach

Otterbach

et al. 2011

Genes Chromosomes & Cancer

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“…[29] However, high frequencies of loss of heterozygosity on 17q12-21 and 13q12-13; [12,30] point to a significant role of these two genes in the pathogenesis of sporadic breast cancer.…”

Section: Discussionmentioning

confidence: 96%

Expression of BRCA1 and BRCA2 proteins and their correlation with clinical staging in breast cancer

Hedau¹,

Batra²,

Singh³

et al. 2015

J Can Res Ther

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“…Our choice of the four BRCA1 alleles analysed in the present study reflects their high prevalence among Polish breast and/or ovarian cancer families and is based on the results of previous research (Brozek et al 2009; Gorski et al 2000; Grzybowska et al 2000; Janiszewska et al 2003; Jasinska and Krzyzosiak 2001; Perkowska et al 2003; Ratajska et al 2008; Van Der Looij et al 2000a, b). …”

Section: Introductionmentioning

confidence: 99%

Prevalence of the most frequent BRCA1 mutations in Polish population

et al. 2011

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The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer.

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Loss of heterozygosity atBRCA1/2 loci in hereditary and sporadic ovarian cancers

Cited by 10 publications

References 17 publications

Loss of heterozygosity proximal to the M6P/IGF2R locus is predictive for the presence of disseminated tumor cells in the bone marrow of ovarian cancer patients before and after chemotherapy

Loss of heterozygosity proximal to the M6P/IGF2R locus is predictive for the presence of disseminated tumor cells in the bone marrow of ovarian cancer patients before and after chemotherapy

Expression of BRCA1 and BRCA2 proteins and their correlation with clinical staging in breast cancer

Prevalence of the most frequent BRCA1 mutations in Polish population

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