Molecular diagnosis of hereditary breast and ovarian cancer (HBOC) by standard methodologies has been limited to the BRCA1 and BRCA2 genes. With the recent development of new sequencing methodologies, the speed and efficiency of DNA testing have dramatically improved. The aim of this work was to validate the use of next-generation sequencing (NGS) for the detection of BRCA1/BRCA2 point mutations in a diagnostic setting and to study the role of other genes associated with HBOC in Portuguese families. A cohort of 94 high-risk families was included in the study, and they were initially screened for the two common founder mutations with variant-specific methods. Fourteen index patients were shown to carry the Portuguese founder mutation BRCA2 c.156_157insAlu, and the remaining 80 were analyzed in parallel by Sanger sequencing for the BRCA1/BRCA2 genes and by NGS for a panel of 17 genes that have been described as involved in predisposition to breast and/or ovarian cancer. A total of 506 variants in the BRCA1/BRCA2 genes were detected by both methodologies, with a 100 % concordance between them. This strategy allowed the detection of a total of 39 deleterious mutations in the 94 index patients, namely 10 in BRCA1 (25.6 %), 21 in BRCA2 (53.8 %), four in PALB2 (10.3 %), two in ATM (5.1 %), one in CHEK2 (2.6 %), and one in TP53 (2.6 %), with 20.5 % of the deleterious mutations being found in genes other than BRCA1/BRCA2. These results demonstrate the efficiency of NGS for the detection of BRCA1/BRCA2 point mutations and highlight the genetic heterogeneity of HBOC.
机构:
Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
Univ British Columbia, Dept Urol Sci, Vancouver, BC V6H 3Z6, CanadaUniv British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
Wyatt, Alexander W.
Mo, Fan
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Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
Univ British Columbia, Dept Urol Sci, Vancouver, BC V6H 3Z6, CanadaUniv British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
Mo, Fan
Wang, Yuzhuo
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Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
Univ British Columbia, Dept Urol Sci, Vancouver, BC V6H 3Z6, Canada
BC Canc Agcy, Dept Expt Therapeut, Vancouver, BC V5Z 1L3, CanadaUniv British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
Wang, Yuzhuo
Collins, Colin C.
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Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
Univ British Columbia, Dept Urol Sci, Vancouver, BC V6H 3Z6, CanadaUniv British Columbia, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
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Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South KoreaSeoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea
Lee, Jung-Yun
Yoon, Jung-Ki
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Seoul Natl Univ, Coll Med, Seoul 110744, South KoreaSeoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea
Yoon, Jung-Ki
Kim, Boyun
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Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110799, South KoreaSeoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea
Kim, Boyun
Kim, Soochi
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Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110799, South KoreaSeoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea
Kim, Soochi
Kim, Min A.
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Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110744, South KoreaSeoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea
Kim, Min A.
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Lim, Hyeonseob
Bang, Duhee
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Yonsei Univ, Dept Chem, Seoul 120749, South KoreaSeoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea
Bang, Duhee
Song, Yong-Sang
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Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea
Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110799, South Korea
Seoul Natl Univ, World Class Univ, Biomodulat, Seoul 151742, South KoreaSeoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea
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Cukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Turan, Ihsan
Erdem, Sevcan
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Cukurova Univ, Dept Pediat, Div Pediat Cardiol, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Erdem, Sevcan
Kotan, Leman Damla
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Cukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Kotan, Leman Damla
Dilek, Semine Ozdemir
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Cukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Dilek, Semine Ozdemir
Tastan, Mehmet
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Cukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Tastan, Mehmet
Gurbuz, Fatih
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Cukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Gurbuz, Fatih
Bisgin, Atil
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机构:
Cukurova Univ, AGENTEM Adana Genet Dis Diag & Treatment Ctr, Adana, Turkey
Cukurova Univ, Dept Med Genet, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Bisgin, Atil
Bayazit, Aysun Karabay
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Cukurova Univ, Dept Pediat, Div Pediat Nephrol, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Bayazit, Aysun Karabay
Topaloglu, Ali Kemal
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Univ Mississippi, Med Ctr, Dept Pediat, Div Pediat Endocrinol, Jackson, MS 39216 USACukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
Topaloglu, Ali Kemal
Yuksel, Bilgin
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Cukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, TurkeyCukurova Univ, Dept Pediat, Div Pediat Endocrinol, Fac Med, Adana, Turkey
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Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USANorthwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
Shah, Ami N.
Davis, Andrew A.
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Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USANorthwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
Davis, Andrew A.
Carroll, Kristen J.
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Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USANorthwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
Carroll, Kristen J.
Wehbe, Firas
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Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USANorthwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
Wehbe, Firas
Behdad, Amir
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Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USANorthwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
Behdad, Amir
Cristofanilli, Massimo
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Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USANorthwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA