Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Validation of CZECANCA (CZEch CAncer paNel for Clinical Application) for targeted NGS-based analysis of hereditary cancer syndromes

J. Soukupova, P. Zemankova, K. Lhotova, M. Janatova, M. Borecka, L. Stolarova, F. Lhota, L. Foretova, E. Machackova, V. Stranecky, S. Tavandzis, P. Kleiblova, M. Vocka, H. Hartmannova, K. Hodanova, S. Kmoch, Z. Kleibl,

. 2018 ; 13 (4) : e0195761. [pub] 20180412

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc18033167

Grant support
NV15-27695A MZ0 CEP Register
NV15-28830A MZ0 CEP Register

BACKGROUND: Carriers of mutations in hereditary cancer predisposition genes represent a small but clinically important subgroup of oncology patients. The identification of causal germline mutations determines follow-up management, treatment options and genetic counselling in patients' families. Targeted next-generation sequencing-based analyses using cancer-specific panels in high-risk individuals have been rapidly adopted by diagnostic laboratories. While the use of diagnosis-specific panels is straightforward in typical cases, individuals with unusual phenotypes from families with overlapping criteria require multiple panel testing. Moreover, narrow gene panels are limited by our currently incomplete knowledge about possible genetic dispositions. METHODS: We have designed a multi-gene panel called CZECANCA (CZEch CAncer paNel for Clinical Application) for a sequencing analysis of 219 cancer-susceptibility and candidate predisposition genes associated with frequent hereditary cancers. RESULTS: The bioanalytical and bioinformatics pipeline was validated on a set of internal and commercially available DNA controls showing high coverage uniformity, sensitivity, specificity and accuracy. The panel demonstrates a reliable detection of both single nucleotide and copy number variants. Inter-laboratory, intra- and inter-run replicates confirmed the robustness of our approach. CONCLUSION: The objective of CZECANCA is a nationwide consolidation of cancer-predisposition genetic testing across various clinical indications with savings in costs, human labor and turnaround time. Moreover, the unified diagnostics will enable the integration and analysis of genotypes with associated phenotypes in a national database improving the clinical interpretation of variants.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18033167
003      
CZ-PrNML
005      
20201023143930.0
007      
ta
008      
181008s2018 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1371/journal.pone.0195761 $2 doi
035    __
$a (PubMed)29649263
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Soukupová, Jana $7 xx0239539 $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
245    10
$a Validation of CZECANCA (CZEch CAncer paNel for Clinical Application) for targeted NGS-based analysis of hereditary cancer syndromes / $c J. Soukupova, P. Zemankova, K. Lhotova, M. Janatova, M. Borecka, L. Stolarova, F. Lhota, L. Foretova, E. Machackova, V. Stranecky, S. Tavandzis, P. Kleiblova, M. Vocka, H. Hartmannova, K. Hodanova, S. Kmoch, Z. Kleibl,
520    9_
$a BACKGROUND: Carriers of mutations in hereditary cancer predisposition genes represent a small but clinically important subgroup of oncology patients. The identification of causal germline mutations determines follow-up management, treatment options and genetic counselling in patients' families. Targeted next-generation sequencing-based analyses using cancer-specific panels in high-risk individuals have been rapidly adopted by diagnostic laboratories. While the use of diagnosis-specific panels is straightforward in typical cases, individuals with unusual phenotypes from families with overlapping criteria require multiple panel testing. Moreover, narrow gene panels are limited by our currently incomplete knowledge about possible genetic dispositions. METHODS: We have designed a multi-gene panel called CZECANCA (CZEch CAncer paNel for Clinical Application) for a sequencing analysis of 219 cancer-susceptibility and candidate predisposition genes associated with frequent hereditary cancers. RESULTS: The bioanalytical and bioinformatics pipeline was validated on a set of internal and commercially available DNA controls showing high coverage uniformity, sensitivity, specificity and accuracy. The panel demonstrates a reliable detection of both single nucleotide and copy number variants. Inter-laboratory, intra- and inter-run replicates confirmed the robustness of our approach. CONCLUSION: The objective of CZECANCA is a nationwide consolidation of cancer-predisposition genetic testing across various clinical indications with savings in costs, human labor and turnaround time. Moreover, the unified diagnostics will enable the integration and analysis of genotypes with associated phenotypes in a national database improving the clinical interpretation of variants.
650    12
$a nádorové biomarkery $7 D014408
650    _2
$a výpočetní biologie $x metody $7 D019295
650    _2
$a variabilita počtu kopií segmentů DNA $7 D056915
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a genetické asociační studie $7 D056726
650    _2
$a genetická predispozice k nemoci $7 D020022
650    _2
$a genetické testování $7 D005820
650    12
$a vysoce účinné nukleotidové sekvenování $x metody $x normy $7 D059014
650    _2
$a lidé $7 D006801
650    _2
$a mutace INDEL $7 D054643
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a mutace $7 D009154
650    _2
$a dědičné nádorové syndromy $x genetika $7 D009386
650    _2
$a reprodukovatelnost výsledků $7 D015203
650    _2
$a senzitivita a specificita $7 D012680
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Zemánková, Petra $7 xx0239540 $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Lhotová, Klára $7 xx0239557 $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Janatova, Marketa $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Borecká, Marianna $7 xx0239525 $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Stolarova, Lenka $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Lhota, Filip $7 xx0239524 $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic. Centre for Medical Genetics and Reproductive Medicine, Gennet, Prague, Czech Republic.
700    1_
$a Foretova, Lenka $u Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
700    1_
$a Machackova, Eva $u Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
700    1_
$a Stranecky, Viktor $u Research Unit for Rare Diseases, Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
700    1_
$a Tavandzis, Spiros, $d 1974- $7 xx0239521 $u Department of Medical Genetics, AGEL Laboratories, AGEL Research and Training Institute, Novy Jicin, Czech Republic.
700    1_
$a Kleiblova, Petra $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
700    1_
$a Vocka, Michal $u Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
700    1_
$a Hartmannova, Hana $u Research Unit for Rare Diseases, Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
700    1_
$a Hodanova, Katerina $u Research Unit for Rare Diseases, Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
700    1_
$a Kmoch, Stanislav $u Research Unit for Rare Diseases, Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
700    1_
$a Kleibl, Zdenek $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
773    0_
$w MED00180950 $t PloS one $x 1932-6203 $g Roč. 13, č. 4 (2018), s. e0195761
856    41
$u https://pubmed.ncbi.nlm.nih.gov/29649263 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20181008 $b ABA008
991    __
$a 20201023143928 $b ABA008
999    __
$a ok $b bmc $g 1340829 $s 1030161
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 13 $c 4 $d e0195761 $e 20180412 $i 1932-6203 $m PLoS One $n PLoS One $x MED00180950
GRA    __
$a NV15-27695A $p MZ0
GRA    __
$a NV15-28830A $p MZ0
LZP    __
$a Pubmed-20181008

Find record

Citation metrics

Archiving options