Search results

1

Increased constitutional chromosome sensitivity to bleomycin in patients with hereditary non polyposis colorectal cancer (HNPCC)

100%

Kladny J., Zajaczek S., Lubinski J.

Journal of Applied Genetics

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1996

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vol. 37

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issue 4

385-392

EN

It has been suggested that mutagen sensitivity is a constitutional factor which may be useful in identification of patients with an increased risk for the development of tumors. In this study, the chromosome sensitivity to bleomycin was measured according to HSU in patients with hereditary non polyposis colorectal cancer (HNPCC), sporadic colorectal cancer and in control persons with no tumor history in family. In vitro lymphocytes were exposed to bleomycin according to HSU and chromosomal damage was quantified by scoring breaks of 100 cells. A significant difference (P < 0.01) in the mean number of breaks per cell (b/c) was found between HNPCC patients (0.59_0.14; n = 12; mean age 55.4 yrs) and control individuals (0.35_0.13: n = 12; mean age 55.8 yrs). In contrast, patients with sporadic colorectal cancer showed a mean b/c value of 0.43_0.14 (n = 14; mean age 63.4 yrs) which was not significantly higher than that in control individuals for this group (0.42 _0.15; n = 14; mean age 63.1 yrs). Selenium protected lymphocytes of HNPCC patients against bleomycin activity in vitro.

2

Constitutional chromosome instability in families with patients affected by sporadic non-hereditary retinoblastoma

100%

Zajaczek S., Gorski B., Krzystolik Z., Lubinski J.

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1999

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vol. 40

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issue 4

343-353

EN

It has been suggested that chromosome instability is a constitutional factor which may be characteristic of families with an increased risk for the development of malignancies. In this study spontaneous chromosome aberrations, sister chromatid exchanges (SCEs) and chromosome sensitivity to bleomycin were analysed in cultured lymphocytes from 13 families with sporadic non-hereditary unilateral retinoblastoma patients. The significantly increased chromosome instability was detected only by the bleomycin test. Higher mean values of breaks/cell were found in all groups of relatives: patients, parents and siblings.

3

The first Rb-1 gene promoter germ-line de novo mutation in patient with retinoblastoma

88%

Zajaczek S., Jakubowska A., Kurzawski G., Krzystolik Z., Lubinski J.

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issue 3

241-247

EN

Rb-1 gene promoter mutations are very rare events, only three retinoblastoma families with such alterations were reported up to now. Herein, we describe the first case of the Rb-1 gene promoter germ, line de novo mutation in a proband with sporadic unilateral retinoblastoma. All of reported Rb-1 gene promoter mutations are associated with a reduced penetrance. Together with the literature data it can be roughly estimated that penetration of cases with alteration localised in promoter and similar as in presented case, is at the level of about 60-70%. It seems, that there are some promoter sites more prone for occurrence of mutations.

4

Molecular analysis of a large novel constitutional deletion in a patient with sporadic unilateral retinoblastoma

76%

Zajaczek S., Cragg H., Jakubowska A., Gorsi B., Krzystolik Z., Cowell J. K., Lubinski J.

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issue 3

233-239

EN

New Rb-1 gene mutation has been studied at sequence level in DNA of peripheral blood lymphocytes DNA. It is a large 137 bp germ-line de novo in-frame deletion involving nearly all of exons 15-16 in a patient with unilateral sporadic retinoblastoma. Analysis of molecular findings suggests that described mutation occurred by non-homologous recombination and slipped mispairing. Possibly this in-frame deletion limited to loss of exons 15-16 is associated with higher prevalence of unilateral tumours.

5

Frequency of mutations related to hereditary haemochromatosis in northwestern Poland

76%

Raszeja-Wyszomirska J., Kurzawski G., Suchy J., Zawada I., Lubinski J., Milkiewicz P.

Journal of Applied Genetics

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2008

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vol. 49

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issue 1

105-107

EN

Hereditary haemochromatosis has been linked with C282Y and H63D mutations of the HFE gene. In Europe, frequencies of these mutations are the highest in Northern European countries and gradually decrease southwards. We analysed the prevalence of HFE mutations in 1517 DNA samples, including 1000 samples from the general population (subjects registered at general practitioner practices) in northwestern Poland, and 517 samples of cord blood from the same region. We identified 2 (0.13%) homozygotes and 117 (7.8%) heterozygotes for the C282Y mutation. As regards the H63D mutation (1505 DNA samples analysed), 38 (2.5%) samples were homozygotes and 380 (25%) were heterozygotes. Twenty-one (1.4%) compound heterozygotes were found. These results correspond well with data from other Central European countries and seem to confirm the hypothesis of North-South spread of the C282Y mutation.

6

Age at diagnosis of cancer as predictor of mutation occurrence in families suspected of HNPCC

76%

Kurzawski G., Debniak D. T., Debniak T., Kladny K. J., Kladny J., Lubinski L. J., Lubinski J.

Journal of Applied Genetics

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2001

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vol. 42

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issue 3

359-366

EN

Analysis of significance of age at cancer diagnosis as a factor allowing identification of a subgroup of patients with a high frequency of hMSH2 and hMLH1 mutations among families that fulfil suspected HNPCC criteria was performed. DNA from thirty-one unrelated patients affected by colorectal cancer from families matching the above criteria were studied by direct sequencing for occurrence of hMSH2 and hMLH1 gene mutations. Seven unequivocal constitutional mutations were detected: five in the hMLH1 gene and two in the hMSH2 gene. Additionally, one hMLH1 alteration of unknown significance was found. All seven mutations were found in a subgroup of 19 patients with cancer diagnosed before the age of 50 years. In a subgroup of 12 patients with cancer diagnosed at an older age only one case with hMLH1 alteration of unknown significance was detected. Our results indicate that early age at cancer diagnosis seems to be a crucial pedigree factor in discrimination of patients with hMSH2 or hMLH1 mutations among families suspected of HNPCC and matching criteria I of ICG-HNPCC.

7

Usefulness of polymorphic markers in exclusion of BRCA1/BRCA2 mutations in families with aggregation of breast/ovarian cancers

64%

Gorski B., Debniak T., Jakubowska A., Cybulski C., Huzarski T., Byrski T., Zlowocka E., Lubinski J.

Journal of Applied Genetics

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2003

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vol. 44

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issue 3

419-423

EN

Founder mutations can account for a large proportion of BRCA1/BRCA2 gene abnormalities in a given population. However there is still a need to study the entire gene in many families, even in countries where founder mutations have been identified. It is possible to decrease the number of cases which are studied by complex and expensive sequencing/Southern blot analyses of BRCA1/BRCA2 genes by exclusion of common BRCA1/BRCA2 alleles in a given family by using polymorphic dinucleotide markers. The goal of our study was to assess the effectiveness of this method in exclusion of BRCA1/BRCA2 constitutional mutations. In each family, blood samples for genetic analyses were taken from two affected relatives from the same generation. Six polymorphic microsatellite markers linked to BRCA1/BRCA2 genes were analysed. Results obtained with these markers were verified by applying BRCA1 testing for the most common founder mutations in Poland and using ?exon by exon? sequencing of coding fragments of the BRCA2 gene. Polymorphic markers useful in BRCA1/BRCA2 analyses included only 3 of 6 examined ? D17S855, D13S260 and D13S267. Occurrence of common alleles of BRCA1 was excluded in 3 families and BRCA2 in 5 out of 30 families. Results obtained by testing for BRCA1 Polish founder mutations and BRCA2 sequencing were in agreement with BRCA1 findings based on polymorphic markers. The only exception was family 994 with BRCA1 exon 5 300T/G mutation, in which BRCA1 mutation carrier was excluded by using D17S855. Among 14 families without BRCA1 Polish founder mutations in this gene were excluded in 2 families and BRCA2 mutation was excluded in one family.

8

Hereditary tumors - prophylactics, early diagnosis, treatment

52%

Lubinski J., Zajaczek S., Kladny J., Kurzawski G., Menkiszak J., Hadaczak P., Cybulski C., Krzystolik K., Toloczko A., Podolski J., Gro

Biotechnologia

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1996

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issue 4

201-207

EN

The authors describe the major rules of prophylactics, survaillance and treatment in patients with high hereditary predispodition for tumors on the basis of the experience of the first Polish hereditary cancer center, which was established in Szczecin in 1992.

9

Ovarian cystadenoma as a characteristic feature of families with hereditary ovarian cancers unassociated with BRCA1 and BRCA2 mutations

52%

Menkiszak J., Brzosko M., Gorski B., Flicinski J., Jakubowska A., Zebielowicz D., Gronwald J., Huzarski T., Byrski T., Teresinski L., Chosia M., Rzepka-Gorska I., Lubinski J.

Journal of Applied Genetics

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2004

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vol. 45

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issue 2

255-263

EN

The study aimed to determine whether hereditary ovarian cancers that are not caused by BRCA1/BRCA2 constitutional mutations are associated with a predisposition to cystadenoma. The study consisted of two parts. Part one concerned the incidence of ovarian cystadenoma in females from families with hereditary ovarian cancer unassociated with BRCA1 mutations. The study group included 62 female patients from 29 families, without any previously diagnosed malignancy, with no proven constitutional mutation of the BRCA1 gene. The first control group was composed of 62 female patients from 53 families, without any previously diagnosed malignancy, with an identified constitutional mutation of the BRCA1 gene. The second control group comprised 124 female patients for whom the only reason for the examination was a prophylactic check-up. All studied women were subjected to intravaginal ultra- sonographic investigations. In 8 patients with benign and/or borderline ovarian cystadenoma, a complete sequencing of coding fragments of the BRCA2 gene from the peripheral blood DNA was performed. Part two of this study concerned the incidence and pattern of malignant tumors in the families of female patients with ovarian cystadenoma. The final study group included 117 patients who had 726 I0 relatives (359 females and 367 males). We concluded that cystadenoma is likely to be a characteristic feature of the subgroup of families with hereditary ovarian cancers unassociated with BRCA1/BRCA2 constitutional mutations.

Refine search results

Increased constitutional chromosome sensitivity to bleomycin in patients with hereditary non polyposis colorectal cancer (HNPCC)

Constitutional chromosome instability in families with patients affected by sporadic non-hereditary retinoblastoma

The first Rb-1 gene promoter germ-line de novo mutation in patient with retinoblastoma

Molecular analysis of a large novel constitutional deletion in a patient with sporadic unilateral retinoblastoma

Frequency of mutations related to hereditary haemochromatosis in northwestern Poland

Age at diagnosis of cancer as predictor of mutation occurrence in families suspected of HNPCC

Usefulness of polymorphic markers in exclusion of BRCA1/BRCA2 mutations in families with aggregation of breast/ovarian cancers

Hereditary tumors - prophylactics, early diagnosis, treatment

Ovarian cystadenoma as a characteristic feature of families with hereditary ovarian cancers unassociated with BRCA1 and BRCA2 mutations