| 1. |
- Helgadottir, Hildur, et al.
(author)
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High risk of tobacco-related cancers in CDKN2A mutation-positive melanoma families.
- 2014
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In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:8, s. 545-552
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Journal article (peer-reviewed)abstract
- Germline mutations in the tumour suppressor gene CDKN2A occur in 5-20% of familial melanoma cases. A single founder mutation, p.Arg112dup, accounts for the majority of CDKN2A mutations in Swedish carriers. In a national program, carriers of p.Arg112dup mutation have been identified. The aim of this study was to assess cancer risks in p.Arg112dup carriers and their first degree relatives (FDRs) and second degree relatives (SDRs).
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| 2. |
- Höiom, Veronica, et al.
(author)
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Hereditary uveal melanoma : A report of a germline mutation in BAP1
- 2013
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In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 52:4, s. 378-384
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Journal article (peer-reviewed)abstract
- Melanoma of the eye is a rare and distinct subtype of melanoma, which only rarely are familial. However, cases of uveal melanoma (UM) have been found in families with mixed cancer syndromes. Here, we describe a comprehensive search for inherited genetic variation in a family with multiple cases of UM but no aggregation of other cancer diagnoses. The proband is a woman diagnosed with UM at 16 years who within 6 months developed liver metastases. We also identified two older paternal relatives of the proband who had died from UM. We performed exome sequencing of germline DNA from members of the affected family. Exome-wide analysis identified a novel loss-of-function mutation in the BAP1 gene, previously suggested as a tumor suppressor. The mutation segregated with the UM phenotype in this family, and we detected a loss of the wild-type allele in the UM tumor of the proband, strongly supporting a causative association with UM. Screening of BAP1 germline mutations in families predisposed for UM may be used to identify individuals at increased risk of disease. Such individuals may then be enrolled in preventive programs and regular screenings to facilitate early detection and thereby improve prognosis.
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| 3. |
- Westermark, Ulrica K, et al.
(author)
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RAD51 can inhibit PDGFB-induced gliomagenesis and genomic instability
- 2011
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In: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 13:12, s. 1277-1287
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Journal article (peer-reviewed)abstract
- Faithful replication and DNA repair are vital for maintenance of genome integrity. RAD51 is a central protein in homologous recombination repair and during replication, when it protects and restarts stalled replication forks. Aberrant RAD51 expression occurs in glioma, and high expression has been shown to correlate with prolonged survival. Furthermore, genes involved in DNA damage response (DDR) are mutated or deleted in human glioblastomas, corroborating the importance of proper DNA repair to suppress gliomagenesis. We have analyzed DDR and genomic instability in PDGF-B-induced gliomas and investigated the role of RAD51 in glioma development. We show that PDGF-B-induced gliomas display genomic instability and that co-expression of RAD51 can suppress PDGF-B-induced tumorigenesis and prolong survival. Expression of RAD51 inhibited proliferation and genomic instability of tumor cells independent of Arf status. Our results demonstrate that the RAD51 pathway can prevent glioma initiation and maintain genome integrity of induced tumors, suggesting reactivation of the RAD51 pathway as a potential therapeutic avenue.
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