Limits...
A Novel WRN Frameshift Mutation Identified by Multiplex Genetic Testing in a Family with Multiple Cases of Cancer.

Yang L, Wang G, Zhao X, Ye S, Shen P, Wang W, Zheng S - PLoS ONE (2015)

Bottom Line: WRN frameshift mutation is considered a potential pathogenic variation according to the guidelines of the American College of Medical Genetics.Other rare non-synonymous germline mutations were also detected in DICER and ELAC2.Our results suggest that the WRN frameshift mutation is important in the surveillance of other members of this family, especially the youngest daughter, but the pathogenicity of the novel WRN frameshift mutation needs to be investigated further.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China; Department of Medical Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, P. R. China.

ABSTRACT
Next-generation sequencing technology allows simultaneous analysis of multiple susceptibility genes for clinical cancer genetics. In this study, multiplex genetic testing was conducted in a Chinese family with multiple cases of cancer to determine the variations in cancer predisposition genes. The family comprises a mother and her five daughters, of whom the mother and the eldest daughter have cancer and the secondary daughter died of cancer. We conducted multiplex genetic testing of 90 cancer susceptibility genes using the peripheral blood DNA of the mother and all five daughters. WRN frameshift mutation is considered a potential pathogenic variation according to the guidelines of the American College of Medical Genetics. A novel WRN frameshift mutation (p.N1370Tfs*23) was identified in the three cancer patients and in the youngest unaffected daughter. Other rare non-synonymous germline mutations were also detected in DICER and ELAC2. Functional mutations in WRN cause Werner syndrome, a human autosomal recessive disease characterized by premature aging and associated with genetic instability and increased cancer risk. Our results suggest that the WRN frameshift mutation is important in the surveillance of other members of this family, especially the youngest daughter, but the pathogenicity of the novel WRN frameshift mutation needs to be investigated further. Given its extensive use in clinical genetic screening, multiplex genetic testing is a promising tool in clinical cancer surveillance.

No MeSH data available.


Related in: MedlinePlus

Sanger sequencing of germline mutations identified in WRN, DICER1, and ELAC2.(A) Sanger sequencing validation of WRN frameshift mutation in each individual. The aligned NGS data of WRN mutation from the mother (I:1). The WRN frameshift mutation presented a 1-bp deletion in chr8:31024663. The bases after A are shown in red, and the A→C point mutation in chr8:31024666 is shown in blue. The WRN frameshift mutation c.4108DelA (p.N1370Tfs*23) was validated by Sanger sequencing in the mother (I:1), the proband (II:1), the second daughter (II:2), and the youngest daughter (II:5); however, it was absent in the other two daughters (II:3 and II:4). (B) The DICER1 missense mutation c.A3334G (p.N1112D) was validated by Sanger sequencing in the mother (I:1) and the second daughter (II:2), but it was absent in the other members of this family. (C) The ELAC2 mutation c.A248G (p.Y83C) was validated by Sanger sequencing in all the members of this family.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4524609&req=5

pone.0133020.g002: Sanger sequencing of germline mutations identified in WRN, DICER1, and ELAC2.(A) Sanger sequencing validation of WRN frameshift mutation in each individual. The aligned NGS data of WRN mutation from the mother (I:1). The WRN frameshift mutation presented a 1-bp deletion in chr8:31024663. The bases after A are shown in red, and the A→C point mutation in chr8:31024666 is shown in blue. The WRN frameshift mutation c.4108DelA (p.N1370Tfs*23) was validated by Sanger sequencing in the mother (I:1), the proband (II:1), the second daughter (II:2), and the youngest daughter (II:5); however, it was absent in the other two daughters (II:3 and II:4). (B) The DICER1 missense mutation c.A3334G (p.N1112D) was validated by Sanger sequencing in the mother (I:1) and the second daughter (II:2), but it was absent in the other members of this family. (C) The ELAC2 mutation c.A248G (p.Y83C) was validated by Sanger sequencing in all the members of this family.

Mentions: We performed Sanger sequencing on the identified germline mutations in WRN, DICER1, and ELAC2. The results of Sanger sequencing were consistent with those of multiplex genetic testing (Fig 2).


A Novel WRN Frameshift Mutation Identified by Multiplex Genetic Testing in a Family with Multiple Cases of Cancer.

Yang L, Wang G, Zhao X, Ye S, Shen P, Wang W, Zheng S - PLoS ONE (2015)

Sanger sequencing of germline mutations identified in WRN, DICER1, and ELAC2.(A) Sanger sequencing validation of WRN frameshift mutation in each individual. The aligned NGS data of WRN mutation from the mother (I:1). The WRN frameshift mutation presented a 1-bp deletion in chr8:31024663. The bases after A are shown in red, and the A→C point mutation in chr8:31024666 is shown in blue. The WRN frameshift mutation c.4108DelA (p.N1370Tfs*23) was validated by Sanger sequencing in the mother (I:1), the proband (II:1), the second daughter (II:2), and the youngest daughter (II:5); however, it was absent in the other two daughters (II:3 and II:4). (B) The DICER1 missense mutation c.A3334G (p.N1112D) was validated by Sanger sequencing in the mother (I:1) and the second daughter (II:2), but it was absent in the other members of this family. (C) The ELAC2 mutation c.A248G (p.Y83C) was validated by Sanger sequencing in all the members of this family.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524609&req=5

pone.0133020.g002: Sanger sequencing of germline mutations identified in WRN, DICER1, and ELAC2.(A) Sanger sequencing validation of WRN frameshift mutation in each individual. The aligned NGS data of WRN mutation from the mother (I:1). The WRN frameshift mutation presented a 1-bp deletion in chr8:31024663. The bases after A are shown in red, and the A→C point mutation in chr8:31024666 is shown in blue. The WRN frameshift mutation c.4108DelA (p.N1370Tfs*23) was validated by Sanger sequencing in the mother (I:1), the proband (II:1), the second daughter (II:2), and the youngest daughter (II:5); however, it was absent in the other two daughters (II:3 and II:4). (B) The DICER1 missense mutation c.A3334G (p.N1112D) was validated by Sanger sequencing in the mother (I:1) and the second daughter (II:2), but it was absent in the other members of this family. (C) The ELAC2 mutation c.A248G (p.Y83C) was validated by Sanger sequencing in all the members of this family.
Mentions: We performed Sanger sequencing on the identified germline mutations in WRN, DICER1, and ELAC2. The results of Sanger sequencing were consistent with those of multiplex genetic testing (Fig 2).

Bottom Line: WRN frameshift mutation is considered a potential pathogenic variation according to the guidelines of the American College of Medical Genetics.Other rare non-synonymous germline mutations were also detected in DICER and ELAC2.Our results suggest that the WRN frameshift mutation is important in the surveillance of other members of this family, especially the youngest daughter, but the pathogenicity of the novel WRN frameshift mutation needs to be investigated further.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China; Department of Medical Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, P. R. China.

ABSTRACT
Next-generation sequencing technology allows simultaneous analysis of multiple susceptibility genes for clinical cancer genetics. In this study, multiplex genetic testing was conducted in a Chinese family with multiple cases of cancer to determine the variations in cancer predisposition genes. The family comprises a mother and her five daughters, of whom the mother and the eldest daughter have cancer and the secondary daughter died of cancer. We conducted multiplex genetic testing of 90 cancer susceptibility genes using the peripheral blood DNA of the mother and all five daughters. WRN frameshift mutation is considered a potential pathogenic variation according to the guidelines of the American College of Medical Genetics. A novel WRN frameshift mutation (p.N1370Tfs*23) was identified in the three cancer patients and in the youngest unaffected daughter. Other rare non-synonymous germline mutations were also detected in DICER and ELAC2. Functional mutations in WRN cause Werner syndrome, a human autosomal recessive disease characterized by premature aging and associated with genetic instability and increased cancer risk. Our results suggest that the WRN frameshift mutation is important in the surveillance of other members of this family, especially the youngest daughter, but the pathogenicity of the novel WRN frameshift mutation needs to be investigated further. Given its extensive use in clinical genetic screening, multiplex genetic testing is a promising tool in clinical cancer surveillance.

No MeSH data available.


Related in: MedlinePlus