Informing patients about their mutation tests : CDKN2A c.256G>A in melanoma as an example

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dc.contributor University of Helsinki, Department of Oncology en
dc.contributor.author Hemminki, Kari
dc.contributor.author Srivastava, Aayushi
dc.contributor.author Rachakonda, Sivaramakrishna
dc.contributor.author Bandapalli, Obul
dc.contributor.author Nagore, Eduardo
dc.contributor.author Hemminki, Akseli
dc.contributor.author Kumar, Rajiv
dc.date.accessioned 2020-09-16T10:13:01Z
dc.date.available 2020-09-16T10:13:01Z
dc.date.issued 2020-07-31
dc.identifier.citation Hemminki , K , Srivastava , A , Rachakonda , S , Bandapalli , O , Nagore , E , Hemminki , A & Kumar , R 2020 , ' Informing patients about their mutation tests : CDKN2A c.256G >A in melanoma as an example ' , Hereditary Cancer in Clinical Practice , vol. 18 , no. 1 , 15 . https://doi.org/10.1186/s13053-020-00146-x en
dc.identifier.issn 1731-2302
dc.identifier.other PURE: 144551638
dc.identifier.other PURE UUID: 237e93d8-99f6-4d56-a8f2-35336f289faa
dc.identifier.other WOS: 000559751800001
dc.identifier.uri http://hdl.handle.net/10138/319394
dc.description.abstract Background When germline mutations are suspected as causal in cancer, patient DNA may be sequenced to detect variants in relevant genes. If a particular mutation has not been reported in reliable family studies, genetic counselors are facing a dilemma of appropriately informing patients. Many sequencing facilities provide an interpretation of the findings based on the available sequence databases or on prediction tools that are curated from bioinformatics and mechanistic datasets. The counseling dilemma is exacerbated if the pedigree data are not informative but the in silico predictions suggest pathogenicity. Methods We present here a real world example of the c.256G > ACDKN2Avariant, which was detected in one melanoma patient where two siblings were diagnosed with melanoma in situ. We investigated a detailed family history of the affected siblings in order to survey probability of the cancer risks within the context to this mutation. Results This c.256G > ACDKN2Avariant was detected in one of the brothers and in the melanoma-free mother while the other brother in the family tested negative. The variant had been previously described in one patient from a melanoma family. In the family under investigation, the mother's 16 first-and second-degree relatives had survived past the median onset age for melanoma and none presented melanoma. We tested the variant using multiple bioinformatic tools that all predicted deleteriousness of the variant. The genetic counseling report to the melanoma patient stated that theCDKN2Avariant was 'likely pathogenic' and the disease was defined as 'likely hereditary melanoma'. Conclusions The pedigree data showed at the most a low penetrance variant, which, if taken into consideration, might have altered the provided diagnosis. When dealing with 'practically' unknown variants the counselors would be advised to incorporate a detailed family history rather than basing predictions on functionality provided by sequencing facilities. en
dc.format.extent 6
dc.language.iso eng
dc.relation.ispartof Hereditary Cancer in Clinical Practice
dc.rights en
dc.subject Genetic counseling en
dc.subject Melanoma suppressor gene en
dc.subject Functionality en
dc.subject Deleteriousness en
dc.subject JOINT-CONSENSUS-RECOMMENDATION en
dc.subject CUTANEOUS MELANOMA en
dc.subject SEQUENCE VARIANTS en
dc.subject CANCER en
dc.subject GENOME en
dc.subject ASSOCIATION en
dc.subject GUIDELINES en
dc.subject STANDARDS en
dc.subject COLLEGE en
dc.subject RISK en
dc.subject 3122 Cancers en
dc.title Informing patients about their mutation tests : CDKN2A c.256G>A in melanoma as an example en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1186/s13053-020-00146-x
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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