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Report on the External Quality Assessment Scheme for Molecular Diagnostics in Korea (2017)
J Lab Med Qual Assur 2018;40:199-210
Published online December 31, 2018
© 2018 Korean Association of External Quality Assessment Service.

Man Jin Kim, Mi-Hye Yoon, Ji Yun Song, Sung Im Cho, Sung-Sup Park, Moon-Woo Seong

Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Correspondence to: Moon-Woo Seong Department of Laboratory Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-4180 Fax: +82-2-747-0359 E-mail: MWSeong@snu.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract

Quality control for genetic analysis has become more important with a drastic increase in testing volume and clinical demands. The molecular diagnostics division of the Korean Association of Quality Assurance for Clinical Laboratory conducted two trials in 2017 on the basis of molecular diagnostics surveys, involving 53 laboratories. The molecular diagnostics surveys included 37 tests: gene rearrangement tests for leukemia (BCR-ABL1, PML-RARA, AML1-ETO, and TEL-AML1), genetic tests for Janus kinase 2, FMS-like tyrosine kinase 3-internal tandem duplication, FMS-like tyrosine kinase 3-tyrosine kinase domain, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2), Avellino (TGFBI), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-raderd Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome, apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, and ABO genotyping. Molecular genetic surveys revealed excellent results for most participants. The external quality assessment program for genetic analysis in 2017 proved useful for continuous education and the evaluation of quality improvement.

Keywords : Laboratory proficiency testing, Molecular pathology, Molecular genetics
꽌 濡

2017뀈룄 遺꾩옄吏꾨떒寃궗 떊鍮숇룄議곗궗뒗 쟾泥 쉶썝湲곌뿉寃 李멸 떊泥議곗궗瑜 븯뿬 珥 2쉶 떆뻾븯怨 쉶李⑤퀎 37醫낅ぉ뿉 媛 2醫낆쓽 寃泥대 李몄뿬湲곌뿉 諛고룷븯뿬 떎뼇븳 룎뿰蹂씠 諛 쑀쟾吏덊솚쓣 룷븿븯떎.

옱猷 諛 諛⑸쾿

1. 遺꾩옄吏꾨떒寃궗

1李 떊鍮숇룄議곗궗뒗 2017뀈 4썡 17씪뿉 寃泥대 諛쒖넚븯怨 2018뀈 1썡 10씪뿉 寃곌낵瑜 넻蹂댄븯怨, 2李 떊鍮숇룄議곗궗뒗 2017뀈 9썡 19씪뿉 寃泥대 諛쒖넚븯怨 2018뀈 2썡 10씪뿉 寃곌낵瑜 넻蹂댄븯떎. 떊鍮숇룄議곗궗 臾쇱쭏쓽 쉶李⑤퀎 寃泥댁 寃泥대쾲샇, 寃泥닿뎄꽦 Table 1怨 媛숇떎.

Table 1 . Survey tests and specimens for external quality assessment of the molecular diagnostics test survey in 2017.

꺿꺿긖estsSpecimens꺿꺿긖est specimens of 1st trialSpecimens꺿꺿긖est specimens of 2nd trial
Leukemia (BCR-ABL1)GH 17-01Normal cell lineGH 17-11Leukemia cell line (BCR/ABL1 positive)
GH 17-02Normal cell lineGH 17-12Normal cell line
Leukemia (PML-RARA)GH 17-01Normal cell lineGH 17-11Normal cell line
GH 17-02Leukemia cell line (PML/RARA positive)GH 17-12Normal cell line
Leukemia (AML1-ETO)GH 17-01Normal cell lineGH 17-11Normal cell line
GH 17-02Normal cell lineGH 17-12Normal cell line
Leukemia (TEL-AML1)GH 17-01Leukemia cell line (TEL/AML1 positive)GH 17-11Normal cell line
GH 17-02Normal cell lineGH 17-12Leukemia cell line (TEL/AML1 positive)
JAK2GH 17-03Extracted DNA with JAK2 mutationGH 17-13Normal DNA
GH 17-04Normal DNAGH 17-14Extracted DNA with JAK2 mutation
FLT3-ITDGH 17-05Normal DNAGH 17-15Normal DNA
GH 17-06Extracted DNA with FLT3-ITD mutationGH 17-16Extracted DNA with FLT3-ITD mutation
FLT3-TKDGH 17-07Extracted DNA with FLT3-TKD mutationGH 17-17Extracted DNA with FLT3-TKD mutation
GH 17-08Normal DNAGH 17-18Normal DNA
NPM1GH 17-09Extracted DNA with NPM1 mutationGH 17-19Normal DNA
GH 17-10Normal DNAGH 17-20Extracted DNA with NPM1 mutation
KRASGS 17-01Extracted DNA with KRAS mutationGS 17-09Normal DNA
GS 17-02Normal DNAGS 17-10Extracted DNA with KRAS mutation
EGFRGS 17-03Extracted DNA with EGFR mutationGS 17-11Extracted DNA with EGFR mutation
GS 17-04Normal DNAGS 17-12Normal DNA
BRAFGS 17-05Normal DNAGS 17-13Extracted DNA with BRAF mutation
GS 17-06Extracted DNA with BRAF mutationGS 17-14Normal DNA
KITGS 17-07Normal DNAGS 17-15Normal DNA
GS 17-08Extracted DNA with KIT mutationGS 17-16Extracted DNA with KIT mutation
BRCA1GG 17-01Extracted DNA with BRCA1 mutationGG 17-41Normal DNA
GG 17-02Normal DNAGG 17-42Extracted DNA with BRCA1 mutation
BRCA2GG 17-03Normal DNAGG 17-43Extracted DNA with BRCA2 mutation
GG 17-04Extracted DNA with BRCA2 mutationGG 17-44Normal DNA
TP53GG 17-05Extracted DNA with TP53 mutationGG 17-45Normal DNA
GG 17-06Normal DNAGG 17-46Extracted DNA with TP53 mutation
ATP7BGG 17-07Extracted DNA with ATP7B mutationGG 17-47Extracted DNA with ATP7B mutation
GG 17-08Normal DNAGG 17-48Normal DNA
MELASGG 17-09Extracted DNA with MELAS mutationGG 17-49Normal DNA
GG 17-10Normal DNAGG 17-50Extracted DNA with MELAS mutation
MERRFGG 17-11Normal DNAGG 17-51Extracted DNA with MERRF mutation
GG 17-12Extracted DNA with MERRF mutationGG 17-52Normal DNA
GJB2GG 17-13Extracted DNA with GJB2 variantGG 17-53Extracted DNA with GJB2 variant
GG 17-14Normal DNAGG 17-54Normal DNA
LHONGG 17-15Extracted DNA with LHON mutationGG 17-55Extracted DNA with LHON mutation
GG 17-16Normal DNAGG 17-56Normal DNA
RETGG 17-17Extracted DNA with RET mutationGG 17-57Extracted DNA with RET mutation
GG 17-18Normal DNAGG 17-58Normal DNA
SCA1GG 17-19Normal DNAGG 17-59Normal DNA
GG 17-20Extracted DNA with SCA1 mutationGG 17-60Normal DNA
SCA2GG 17-19Normal DNAGG 17-59Normal DNA
GG 17-20Normal DNAGG 17-60Normal DNA
SCA3GG 17-19Normal DNAGG 17-59Normal DNA
GG 17-20Normal DNAGG 17-60Normal DNA
SCA6GG 17-19Normal DNAGG 17-59Extracted DNA with SCA6 mutation
GG 17-20Normal DNAGG 17-60Normal DNA
SCA7GG 17-19Normal DNAGG 17-59Normal DNA
GG 17-20Normal DNAGG 17-60Normal DNA
APOE genotypeGG 17-21Extracted DNA with APOE 琯3/琯3 genotypeGG 17-61Extracted DNA with APOE 琯4/琯4 genotype
GG 17-22Extracted DNA with APOE 琯4/琯4 genotypeGG 17-62Extracted DNA with APOE 琯3/琯4 genotype
AchondroplasiaGG 17-23Normal DNAGG 17-63Extracted DNA with FGFR3 mutation
GG 17-24Extracted DNA with FGFR3 mutationGG 17-64Normal DNA
MTHFR genotypeGG 17-25Extracted DNA with MTHFR 677T/T homozygoteGG 17-65Extracted DNA with MTHFR 677C/T heterozygous
GG 17-26Normal DNAGG 17-66Extracted DNA with MTHFR 677T/T homozygote
PWS/ASGG 17-27Normal DNAGG 17-67Extracted DNA with PWS mutation
GG 17-28Extracted DNA with AS mutationGG 17-68Normal DNA
DMDGG 17-29Normal DNAGG 17-69Extracted DNA with DMD mutation
GG 17-30Extracted DNA with DMD mutationGG 17-70Normal DNA
HDGG 17-31Extracted DNA with HD mutationGG 17-71Extracted DNA with HD mutation
GG 17-32Normal DNAGG 17-72Normal DNA
FMR1GG 17-33Normal DNAGG 17-73Normal DNA
GG 17-34Extracted DNA with FMR1 mutationGG 17-74Extracted DNA with FMR1 mutation
TGFBIGG 17-35Extracted DNA with TGFBI mutationGG 17-75Normal DNA
GG 17-36Normal DNAGG 17-76Extracted DNA with TGFBI mutation
SBMAGG 17-37Normal DNAGG 17-77Normal DNA
GG 17-38Extracted DNA with AR mutationGG 17-78Extracted DNA with AR mutation
SMAGG 17-39Extracted DNA with SMN1 mutationGG 17-79Extracted DNA with SMN1 mutation
GG 17-40Normal DNAGG 17-80Normal DNA
ABO genotypeGO 17-01Extracted DNA with cis-AB/B genotypeGO 17-03Extracted DNA with B/O genotype
GO 17-02Extracted DNA with A/O genotypeGO 17-04Extracted DNA with cis-AB/A genotype

Abbreviations: JAK2, Janus kinase 2; FLT3, FMS-like tyrosine kinase 3; ITD, internal tandem duplication; TKD, tyrosine kinase domain; NPM1, nucleophosmin; EFGR, epidermal growth factor receptor; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MERRF, myoclonic epilepsy with ragged red fibres; LHON, Leber hereditary optic neuropathy; RET, multiple endocrine neoplasia 2; SCA, spinocerebellar ataxia; APOE, apolipoprotein E; MTHFR, methylenetetrahydrofolate reductase; PWS/AS, Prader-Willi/Angelman syndrome; DMD, Duchenne muscular dystrophy; HD, Huntington disease; FMR1, fragile X mental retardation-1; TGFBI, transforming growth factor beta induced; SBMA, spinal and bulbar muscular atrophy; SMA, spinal muscular atrophy..


媛 湲곌쓽 蹂닿퀬뿉 뵲씪 寃궗諛⑸쾿, 寃궗寃곌낵 諛 寃궗諛⑸쾿蹂 寃궗寃곌낵瑜 鍮꾧탳 遺꾩꽍븯쑝硫 湲곌蹂 蹂닿퀬寃곌낵뿉 븯뿬 湲곕낯쟻씤 룊媛(acceptable, unacceptable)瑜 떎떆븯떎. 빀寃/遺덊빀寃⑹쓽 湲곗 10湲곌 誘몃쭔쓽 李몄뿬빆紐⑹쓽 寃쎌슦 二쇨湲곌쓽 寃利앷껐怨쇱 씪移섑븯뒗 寃쎌슦 acceptable씠씪怨 뙋젙븯쑝硫 10湲곌 씠긽쓽 李몄뿬빆紐⑹쓽 寃쎌슦 二쇨湲곌쓽 寃利앷껐怨쇱 李몄뿬湲곌 以 80% 씠긽쓽 씪移섍 엳쓣 寃쎌슦 acceptable씠씪怨 뙋젙븯떎. 궪뿼湲 諛섎났 쑀쟾吏덊솚씤 Huntington disease (HD), spinocerebellar ataxia (SCA1, SCA2, SCA3, SCA6, SCA7), spinal and bulbar muscular atrophy (SBMA), fragile X syndrome (FMR1) 寃궗쓽 젙웾媛믪 룊媛뿉 룷븿떆궎吏 븡븯떎.

寃 怨

1. 遺꾩옄吏꾨떒寃궗

1) 李몄뿬湲곌 諛 寃궗빆紐

2017뀈 1李 諛 2李 떊鍮숇룄議곗궗뿉 李몄뿬븳 湲곌 53媛 湲곌씠뿀떎. 遺꾩옄吏꾨떒寃궗뒗 삁븸醫낆뼇 8醫낅ぉ, 怨좏삎醫낆뼇 4醫낅ぉ, 꽑泥쒖꽦 쑀쟾吏덊솚 8醫낅ぉ, 誘명넗肄섎뱶由ъ븘 쑀쟾吏덊솚 3醫, 궪뿼湲 諛섎났 쑀쟾吏덊솚 7醫, 떊寃쎄렐쑁 쑀쟾吏덊솚 1醫, 湲고 쑀쟾吏덊솚 3醫, 쑀쟾삎寃궗 3醫낅ぉ 벑 珥 37醫낅ぉ뿉 빐 떆뻾븯떎.

삁븸醫낆뼇 遺꾩옄吏꾨떒寃궗 8醫낅ぉ씤 leukemia and lymphomas (BCR-ABL1, PML-RARA, AML1-ETO, TEL-AML1), JAK2, FMS-like tyrosine kinase 3 (FLT3-internal tandem duplication [ITD], FLT3-tyrosine kinase domain [TKD]), nucleophosmin (NPM1) 遺꾩옄吏꾨떒寃궗뒗 1李⑥뿉꽌 媛곴컖 36湲곌, 34湲곌, 33湲곌, 31湲곌, 30湲곌, 19湲곌, 17湲곌, 16湲곌씠, 2李⑥뿉꽌 37湲곌, 36湲곌, 35湲곌, 33湲곌, 31湲곌, 20湲곌, 18湲곌, 18湲곌씠 李멸븯떎. 怨좏삎醫낆뼇 遺꾩옄吏꾨떒寃궗 4醫낅ぉ씤 KRAS, BRAF, EGFR, KIT 遺꾩옄吏꾨떒寃궗뒗 1李⑥뿉꽌 10湲곌, 15湲곌, 9湲곌, 10湲곌씠 李멸븯怨, 2李⑥뿉꽌뒗 11湲곌, 14湲곌, 10湲곌, 10湲곌씠 李멸븯떎. 쑀쟾吏덊솚 8醫낅ぉ씤 BRCA1, BRCA2, TP53, ATP7B, FGFR3, GJB2, TGFBI, RET 遺꾩옄吏꾨떒寃궗뒗 1李⑥뿉꽌 媛곴컖 16湲곌, 16湲곌, 6湲곌, 8湲곌, 9湲곌, 10湲곌, 13湲곌, 7湲곌씠 李멸븯쑝硫, 2李⑥뿉꽌 15湲곌, 15湲곌, 6湲곌, 8湲곌, 9湲곌, 10湲곌, 13湲곌, 7湲곌씠 李멸븯떎. 궪뿼湲 諛섎났 쑀쟾吏덊솚怨 떊寃쎄렐쑁 쑀쟾吏덊솚 醫낅ぉ씤 HD, SCA1, SCA2, SCA3, SCA6, SCA7, SBMA, FMR1 遺꾩옄吏꾨떒寃궗뿉뒗 1李⑥뿉꽌 媛곴컖 5湲곌, 6湲곌, 7湲곌, 6湲곌, 6湲곌, 6湲곌, 5湲곌, 10湲곌씠 李멸븯怨, 2李⑥뿉꽌 5湲곌, 6湲곌, 7湲곌, 6湲곌, 6湲곌, 6湲곌, 5湲곌, 10湲곌씠 李멸븯떎. 誘명넗肄섎뱶由ъ븘 쑀쟾吏덊솚뿉 냽븯뒗 醫낅ぉ씤 mitochondrial encephalopathy with lactic acidosis and stroke like episodes (MELAS), myoclonic epilepsy ragged red fibre (MERRF), Leber hereditary optic neuropathy (LHON굥major mutation) 寃궗뿉뒗 1李⑥뿉꽌 媛곴컖 6湲곌, 5湲곌, 6湲곌씠 李멸븯怨, 2李⑥뿉꽌 6湲곌, 5湲곌, 6湲곌씠 媛곴컖 李멸븯떎. Prader-Willi/Angelman syndrome (PWS/AS), Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA) 遺꾩옄吏꾨떒寃궗뒗 1李⑥뿉꽌 媛곴컖 5湲곌, 6湲곌, 6湲곌씠 媛곴컖 李멸븯怨, 2李⑥뿉꽌 5湲곌, 6湲곌, 6湲곌씠 媛곴컖 李멸븯떎. 쑀쟾삎寃궗뿉 냽븯뒗 醫낅ぉ씤 apolipoprotein E (APOE) genotyping, methylenetetrahydro-folate reductase (MTHFR) genotyping, ABO genotyping 遺꾩옄吏꾨떒寃궗뒗 1李⑥뿉꽌 媛곴컖 32湲곌, 13湲곌, 13湲곌씠 李멸븯쑝硫, 2李⑥뿉꽌 34湲곌, 14湲곌, 13湲곌씠 李멸븯떎.

2) 寃궗諛⑸쾿

媛 湲곌蹂 궗슜븯뒗 寃궗踰뺤 Table 2 媛숇떎.

Table 2 . Mutation detection methods of the molecular diagnostics test survey in 2017.

꺿꺿긖ests긎utation detection methods (lab-developed test)ResponseMutation detection methods (commercial kit)Response
Leukemia (BCR-ABL1)Allele-specific PCR1Hemavision29
PCR (include multiplex), gel electrophoresis1
PCR and gel electrophoresis2
Real-time PCR4
Leukemia (PML-RARA)Allele-specific PCR1Hemavision29
PCR (include multiplex), gel electrophoresis1
PCR and gel electrophoresis2
Real-time PCR3
Leukemia (AML1-ETO)Allele-specific PCR1Hemavision29
PCR (include multiplex), gel electrophoresis1
PCR and gel electrophoresis2
Real-time PCR2
Leukemia (TEL-AML1)Allele-specific PCR1Hemavision29
PCR (include multiplex), gel electrophoresis1
PCR and gel electrophoresis2
JAK2Allele-specific PCR7
Pyrosequencing1
Real-time PCR10
Real-time PCR, hydrolysis probe2
Sanger sequencing10
Single base extension (SNaPshot)1
FLT3-ITDAllele-specific PCR1
PCR and fluorescent based capillary electrophoresis (fragment length analysis)3
PCR (include multiplex), gel electrophoresis1
PCR and gel electrophoresis1
RFLP1
Sanger sequencing12
FLT3-TKDAllele-specific PCR1
PCR and fluorescent based capillary electrophoresis (fragment length analysis)1
PCR (include multiplex), gel electrophoresis1
PCR and gel electrophoresis10
Sanger sequencing2
Other*2
NPM1Real-time PCR1
RFLP1
Sanger sequencing16
KRASCodon12-pyrosequencing2
Codon13-pyrosequencing2
Codon61-pyrosequencing2
Codon12-Sanger sequencing8
Codon13-Sanger sequencing8
Codon61-Sanger sequencing8
BRAFcodon 600 (p.V600E)-pyrosequencing2
codon 600 (p.V600E)-real-time PCR6
codon 600 (p.V600E)-real-time PCR, hydrolysis probe3
codon 600 (p.V600E)-Sanger sequencing4
codon 600 (p.V600K)-pyrosequencing2
codon 600 (p.V600K)-Sanger sequencing4
codon 600 (p.V600K)-pyrosequencing2
codon 600 (p.V600K)-Sanger sequencing4
EGFRCodon719-pyrosequencing1
Codon790-pyrosequencing1
Codon858-pyrosequencing1
Codon861-pyrosequencing1
Exon 19 deletion-pyrosequencing1
Codon719-Sanger sequencing8
Codon790-Sanger sequencing8
Codon858-Sanger sequencing8
Codon861-Sanger sequencing8
Exon 19 deletion-Sanger sequencing8
KITcodon 816-real-time PCR, hydrolysis probe1
codon 816-Sanger sequencing8
codon 816-other1
Exon 9-Sanger sequencing6
Exon 9-other1
Exon 11-Sanger sequencing6
Exon 11-other1
Exon 13-Sanger sequencing6
Exon 13-other1
Exon 17-Sanger sequencing7
Exon 17-other1
BRCA1Sanger sequencing16
BRCA2Sanger sequencing16
TP53Sanger sequencing6
ATP7BSanger sequencing8
AchondroplasiaSanger sequencing9
GJB2Sanger sequencing10
TGFBIReal-time PCR3
Sanger sequencing10
RETSanger sequencing7
HDPCR and fluorescent based capillary electrophoresis (fragment length analysis)5
SCA1PCR and fluorescent based capillary electrophoresis (fragment length analysis)6
SCA2PCR and fluorescent based capillary electrophoresis (fragment length analysis)7
SCA3PCR and fluorescent based capillary electrophoresis (fragment length analysis)6
SCA6PCR and fluorescent based capillary electrophoresis (fragment length analysis)6
SCA7PCR and fluorescent based capillary electrophoresis (fragment length analysis)6
SBMAPCR and fluorescent based capillary electrophoresis (fragment length analysis)5
LHONSanger sequencing5
Single base extension (SNaPshot)1
MELASSanger sequencing6
MERRFSanger sequencing5
PWS/ASPCR and gel electrophoresis, methylation specific5
DMDMLPA6
SMAMLPA4
RFLP2
APOE genotypeAllele-specific PCR5
PCR (include multiplex), gel electrophoresis3
PCR and gel electrophoresis1
Real-time PCR17
Real-time PCR, hydrolysis probe1
Real-time PCR, melting curve analysis1
RFLP1
Sanger sequencing2
Line probe assay1
MTHFR genotypeAllele-specific PCR2
PCR and gel electrophoresis1
Real-time PCR1
Real-time PCR, hydrolysis probe1
Real-time PCR, melting curve analysis1
RFLP4
Sanger sequencing2
Single base extension (SNaPshot)1
ABO genotypeAllele-specific PCR1
RFLP1
Sanger sequencing9
Single base extension (SNaPshot)2
FMR1PCR and fluorescent based capillary electrophoresis (fragment length analysis)6
Southern blot1
Triplet repeat primed PCR and fluorescent based capillary electrophoresis2

Abbreviations: PCR, polymerase chain reaction; JAK2, Janus kinase 2; FLT3, FMS-like tyrosine kinase 3; ITD, internal tandem duplication; RFLP, restriction fragment length polymorphism; TKD, tyrosine kinase domain; NPM1, nucleophosmin; EFGR, epidermal growth factor receptor; RET, multiple endocrine neoplasia 2; HD, Huntington disease; SCA, spinocerebellar ataxia; SBMA, spinal and bulbar muscular atrophy; LHON, Leber hereditary optic neuropathy; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MERRF, myoclonic epilepsy with ragged red fibres; PWS/AS, Prader-Willi/Angelman syndrome; DMD, Duchenne muscular dystrophy; MLPA, multiple ligation probe amplification; SMA, spinal muscular atrophy; APOE, apolipoprotein E; MTHFR, methylenetetrahydrofolate reductase; FMR1, fragile X mental retardation-1..

*No response.


3) 떊鍮숇룄議곗궗 寃곌낵

Leukemia and lymphomas 遺꾩옄吏꾨떒寃궗뒗 1李⑥뿉꽌 TEL-AML1 옱諛곗뿴怨 PML-RARA 옱諛곗뿴 寃泥대, 2李⑥뿉꽌뒗 TEL-AML1 옱諛곗뿴怨 BCR-ABL1 옱諛곗뿴 寃泥대줈 援ъ꽦븯떎. 1李 룊媛뿉꽌 PML-RARA, AML1-ETO 옱諛곗뿴 臾명빆뿉 븯뿬 李몄뿬븳 紐⑤뱺 湲곌씠 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯怨, BCR-ABL1 옱諛곗뿴 臾명빆 1媛 湲곌씠 떎瑜 subtype쓣 蹂닿퀬븯떎. TEL-AML1 옱諛곗뿴 臾명빆 31媛 湲곌 以 1媛 湲곌씠 삁긽寃곌낵 긽씠븳 寃곌낵瑜 蹂닿퀬븯떎. 2李⑥뿉꽌뒗 BCR-ABL1, PML-RARA, AML1-ETO 옱諛곗뿴 臾명빆뿉 븯뿬 李몄뿬븳 紐⑤뱺 湲곌씠 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯怨 TEL-AML1 옱諛곗뿴 臾명빆 33媛 湲곌 以 2媛 湲곌씠 삁긽寃곌낵 긽씠븳 寃곌낵瑜 蹂닿퀬븯떎.

JAK2, FLT3-ITD, FLT3-TKD, NPM1 遺꾩옄吏꾨떒寃궗뿉꽌뒗 JAK2, NPM1뿉 李몄뿬븳 紐⑤뱺 湲곌씠 1李⑥ 2李⑥뿉꽌 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. FLT3-ITD 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉 李몄뿬븳 紐⑤뱺 湲곌씠 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯쑝굹 2李⑥뿉꽌뒗 1媛 湲곌씠 젙긽 寃泥댁뿉꽌 蹂씠瑜 諛쒓껄빐 蹂닿퀬븯쑝硫 FLT3-TKD 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉꽌 1媛 湲곌씠 蹂씠瑜 諛쒓껄븯吏 紐삵븯쑝硫 2李⑥뿉꽌뒗 쟾泥 쓳떟寃곌낵쓽 80% 씠긽쓽 consensus瑜 蹂댁씠吏 븡븘 쟾泥 湲곌쓽 寃곌낵瑜 쐕ngraded앸줈 蹂닿퀬븯떎.

KRAS, BRAF, EGFR, KIT 遺꾩옄吏꾨떒寃궗뿉꽌뒗 KRAS, BRAF, EGFR 遺꾩옄吏꾨떒寃궗뿉 李몄뿬븳 紐⑤뱺 湲곌씠 1李⑥ 2李⑥뿉꽌 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. KIT 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉꽌 1媛 湲곌씠 삁긽寃곌낵 긽씠븳 寃곌낵瑜 蹂닿퀬븯怨 2李⑥뿉꽌뒗 紐⑤뱺 湲곌씠 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎.

BRCA1, BRCA2, TP53, ATP7B, GJB2, FGFR3, TGFBI, RET 遺꾩옄吏꾨떒寃궗뿉꽌뒗 BRCA2, TP53, FGFR3, TGFBI뿉 李몄뿬븳 紐⑤뱺 湲곌씠 1李⑥ 2李⑥뿉꽌 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. BRCA1 遺꾩옄吏꾨떒寃궗뿉꽌뒗 2李⑥뿉 李몄뿬湲곌 以 1媛 湲곌씠 삁긽寃곌낵 떎瑜 뿼湲곕씠瑜 蹂닿퀬븯떎. ATP7B 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉 李몄뿬븳 1媛 湲곌씠 삁긽 蹂씠遺쐞 긽씠븳 遺쐞쓽 蹂씠瑜 蹂닿퀬븯쑝굹 2李⑥뿉꽌뒗 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. GJB2 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥ 2李⑥뿉 李몄뿬븳 媛 1媛 湲곌씠 삁긽 蹂씠遺쐞 긽씠븳 遺쐞쓽 蹂씠瑜 蹂닿퀬븯뿬 룊媛뿉꽌 젣쇅릺뿀떎. RET 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉꽌 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯쑝굹 2李⑥뿉꽌뒗 1媛 湲곌씠 삁긽寃곌낵 떎瑜 떒諛깆쭏蹂씠瑜 蹂닿퀬븯떎.

HD, SCA1, SCA2, SCA3, SCA6, SCA7, SBMA 遺꾩옄吏꾨떒寃궗뿉꽌뒗 SCA1, SCA2, SCA3, SCA6, SCA7 遺꾩옄吏꾨떒寃궗뿉 李몄뿬븳 紐⑤뱺 湲곌씠 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. HD, SBMA 遺꾩옄吏꾨떒寃궗뿉꽌뒗 2李⑥뿉 李몄뿬븳 湲곌 以 媛곴컖 2媛 湲곌씠 삁긽寃곌낵 긽씠븳 寃곌낵瑜 蹂닿퀬븯떎.

MELAS, MERRF, LHON 遺꾩옄吏꾨떒寃궗뿉꽌뒗 MERRF, LHON 遺꾩옄吏꾨떒寃궗뿉 李몄뿬븳 紐⑤뱺 湲곌뿉꽌 1李⑥ 2李⑥뿉꽌 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. MELAS 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉꽌 1媛 湲곌씠 삁긽寃곌낵 긽씠븳 寃곌낵瑜 蹂닿퀬븯쑝굹 2李⑥뿉꽌뒗 李몄뿬븳 紐⑤뱺 湲곌뿉꽌 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. PWS/AS, DMD, SMA 遺꾩옄吏꾨떒寃궗뿉꽌뒗 李몄뿬븳 紐⑤뱺 湲곌씠 1李⑥ 2李⑥뿉꽌 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎.

APOE, MTHFR, ABO genotyping 遺꾩옄吏꾨떒寃궗뿉꽌뒗 MTHFR genotyping 遺꾩옄吏꾨떒寃궗뿉 李몄뿬븳 紐⑤뱺 湲곌씠 1李⑥ 2李⑥뿉꽌 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. APOE genotyping 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉 젣怨듯븳 1踰 寃泥댁뿉 븯뿬 1媛 湲곌씠 삁긽寃곌낵 긽씠븳 寃곌낵瑜 蹂닿퀬븯떎. ABO genotyping 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉 젣怨듯븳 1踰 寃泥댁뿉 븯뿬 2媛 湲곌씠 삁긽寃곌낵 긽씠븳 寃곌낵瑜 蹂닿퀬븯쑝硫 2踰 寃泥댁뿉 븯뿬 1媛 湲곌씠 삁긽寃곌낵 긽씠븳 寃곌낵瑜 蹂닿퀬븯떎.

FMR1 遺꾩옄吏꾨떒寃궗뿉꽌뒗 1李⑥뿉 李몄뿬븳 1媛 湲곌씠 룊媛슜 寃泥대줈 젣怨듯븳 2醫낅쪟쓽 寃泥 紐⑤몢뿉꽌 삁긽寃곌낵 떎瑜 寃곌낵瑜 蹂닿퀬븯쑝굹 2李⑥뿉꽌뒗 李몄뿬븳 紐⑤뱺 湲곌씠 삁긽寃곌낵 씪移섑븯뒗 寃곌낵瑜 蹂닿퀬븯떎. 媛 湲곌蹂 蹂닿퀬寃곌낵瑜 젙由ы븳 젙삤떟 넻怨꾨뒗 Table 3怨 媛숇떎.

Table 3 . Results of the molecular diagnostics test survey carried out in 2017.

꺿꺿긖estsSpecimens of 1st trial꺿꺿긆ntended responsesTotal no. of participants/acceptable responseSpecimens of 2nd trial꺿꺿긆ntended responsesTotal no. of participants/acceptable response
Leukemia (BCR-ABL1)GH 17-01Mutation not detected36/36GH 17-11BCR/ABL1 positive37/37
GH 17-02Mutation not detected36/36GH 17-12Mutation not detected37/37
Leukemia (PML-RARA)GH 17-01Mutation not detected34/34GH 17-11Mutation not detected36/36
GH 17-02PML/RARA positive34/34GH 17-12Mutation not detected36/36
Leukemia (AML1-ETO)GH 17-01Mutation not detected33/33GH 17-11Mutation not detected35/35
GH 17-02Mutation not detected33/33GH 17-12Mutation not detected35/35
Leukemia (TEL-AML1)GH 17-01TEL/AML1 positive31/30GH 17-11Mutation not detected33/33
GH 17-02Mutation not detected31/31GH 17-12TEL/AML1 positive33/31
JAK2GH 17-03p.Val617Phe mutation30/30GH 17-13Mutation not detected31/31
GH 17-04Mutation not detected30/30GH 17-14p.Val617Phe mutation31/31
FLT3-ITDGH 17-05Mutation not detected19/19GH 17-15Mutation not detected20/19
GH 17-06FLT3-ITD mutation19/19GH 17-16FLT3-ITD mutation20/20
FLT3-TKDGH 17-07FLT3- TKD mutation17/16GH 17-17FLT3-TKD mutation18/all ungraded
GH 17-08Mutation not detected17/17GH 17-18Mutation not detected18/18
NPM1GH 17-09NPM1 mutation16/16GH 17-19Mutation not detected18/18
GH 17-10Mutation not detected16/16GH 17-20NPM1 mutation18/18
KRASGS 17-01Codon 12 mutation10/10GS 17-09Mutation not detected11/11
GS 17-02Mutation not detected10/10GS 17-10Codon 12 mutation11/11
EGFRGS 17-03Exon 19 deletion9/9GS 17-11Exon 19 deletion10/10
GS 17-04Mutation not detected9/9GS 17-12EGFR mutation10/10
BRAFGS 17-05Mutation not detected15/15GS 17-13p.Val600Glu14/14
GS 17-06p.Val600Glu15/15GS 17-14Mutation not detected14/14
KITGS 17-07Mutation not detected10/10GS 17-15Mutation not detected10/10
GS 17-08Codon 816 mutation10/9GS 17-16Codon 816 Mutation12/12
BRCA1GG 17-01c.5074+1G>T, heterozygote16/16GG 17-41Mutation not detected15/15
GG 17-02Mutation not detected16/16GG 17-42c.3442delG, p.Glu1148Argfs*7, heterozygote15/14
BRCA2GG 17-03Mutation not detected16/16GG 17-43Mutation not detected15/15
GG 17-04c.8140C>T, p.Gln2714*, heterozygote16/16GG 17-44c.7480C>T, p.Arg2494*, heterozygote15/15
TP53GG 17-05c.742C>T, p.Arg248Trp, heterozygote6/6GG 17-45Mutation not detected6/6
GG 17-06Mutation not detected6/6GG 17-46c.742C>T, p.Arg248Trp, heterozygote6/6
ATP7BGG 17-07c.3809A>G, p.Asn1270Ser, heterozygote c.3247C>T, p.Leu1083Phe, heterozygote8/7GG 17-47c.3104G>T, p.Gly1035Val, heterozygotec.3247C>T, p.Leu1083Phe, heterozygote8/8
GG 17-08Mutation not detected8/8GG 17-48Mutation not detected8/8
MELASGG 17-09m.3243A>G6/5GG 17-49Mutation not detected6/6
GG 17-10Mutation not detected6/6GG 17-50m.3243A>G6/6
MERRFGG 17-11Mutation not detected5/5GG 17-51m.8344A>G5/5
GG 17-12m.8344A>G5/5GG 17-52Mutation not detected5/5
GJB2GG 17-13c.35delG, p.Gly12Valfs*, heterozygote10/9GG 17-53c.35delG, p.Gly12Valfs*, heterozygote10/10
GG 17-14Mutation not detected10/10GG 17-54Mutation not detected10/10
LHONGG 17-15m.11778G>A6/6GG 17-55Mutation not detected6/6
GG 17-16Mutation not detected6/6GG 17-56m.11778G>A6/6
RETGG 17-17c.2753T>C, p.Met918Thr, heterozygote7/7GG 17-57c.1859G>C, p.Cys620Ser, heterozygote7/6
GG 17-18Mutation not detected7/7GG 17-58Mutation not detected7/7
SCA1GG 17-19Mutation not detected6/6GG 17-59Mutation not detected6/6
GG 17-20SCA1 mutation6/6GG 17-60Mutation not detected6/6
SCA2GG 17-19Mutation not detected7/7GG 17-59Mutation not detected7/7
GG 17-20Mutation not detected7/7GG 17-60Mutation not detected7/7
SCA3GG 17-19Mutation not detected6/6GG 17-59Mutation not detected6/6
GG 17-20Mutation not detected6/6GG 17-60Mutation not detected6/6
SCA6GG 17-19Mutation not detected6/6GG 17-59SCA6 mutation6/6
GG 17-20Mutation not detected6/6GG 17-60Mutation not detected6/6
SCA7GG 17-19Mutation not detected6/6GG 17-59Mutation not detected6/6
GG 17-20Mutation not detected6/6GG 17-60Mutation not detected6/6
APOE genotypeGG 17-21APOE 琯3/琯3 genotype32/31GG 17-61APOE 琯4/琯4 genotype34/34
GG 17-22APOE 琯4/琯4 genotype32/31GG 17-62APOE 琯3/琯4 genotype34/34
AchondroplasiaGG 17-23Mutation not detected9/9GG 17-63p.Gly380Arg9/9
GG 17-24p.Gly380Arg9/9GG 17-64Mutation not detected9/9
MTHFR genotypeGG 17-25MTHFR 677T/T homozygous genotype13/13GG 17-65MTHFR 677C/T heterozygous genotype14/14
GG 17-26Mutation not detected13/13GG 17-66MTHFR 677T/T homozygous genotype14/14
PWS/ASGG 17-27Mutation not detected5/5GG 17-67Prader-Willi syndrome5/5
GG 17-28Angelman syndrome5/5GG 17-68Mutation not detected5/5
DMDGG 17-29Mutation not detected6/6GG 17-69Exon 56-57 deletion6/6
GG 17-30Exon 18-44 deletion6/6GG 17-70Mutation not detected6/6
HDGG 17-31Full penetrance5/5GG 17-71Full penetrance5/5
GG 17-32Mutation not detected5/5GG 17-72Mutation not detected5/3
FMR1GG 17-33Full mutation10/9GG 17-73Mutation not detected10/10
GG 17-34Mutation not detected10/9GG 17-74Full mutation10/10
TGFBIGG 17-35p.Arg124His13/13GG 17-75Mutation not detected13/13
GG 17-36Mutation not detected13/13GG 17-76p.Arg124His13/13
SBMAGG 17-37Mutation not detected5/5GG 17-77Full penetrance5/3
GG 17-38Full penetrance5/5GG 17-78Mutation not detected5/5
SMAGG 17-39SMN1, Exon7, homozygous deletion6/6GG 17-79SMN1, Exon7, homozygous deletion6/6
GG 17-40Mutation not detected6/6GG 17-80Mutation not detected6/6
ABO genotypeGO 17-01cis-AB/B genotype13/11GO 17-03B/O genotype13/13
GO 17-02A/O genotype13/12GO 17-04cis-AB/A genotype13/13

Abbreviations: FLT3, FMS-like tyrosine kinase 3; ITD, internal tandem duplication; TKD, tyrosine kinase domain; NPM1, nucleophosmin; EFGR, epidermal growth factor receptor; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MERRF, myoclonic epilepsy with ragged red fibres; LHON, Leber hereditary optic neuropathy; RET, multiple endocrine neoplasia 2; SCA, spinocerebellar ataxia; APOE, apolipoprotein E; MTHFR, methylenetetrahydrofolate reductase; PWS/AS, Prader-Willi/Angelman syndrome; DMD, Duchenne muscular dystrophy; HD, Huntington셲 disease; FMR1, fragile X mental retardation-1; TGFBI, transforming growth factor beta induced; SBMA, spinal and bulbar muscular atrophy; SMA, spinal muscular atrophy..


怨 李

2017뀈룄 遺꾩옄吏꾨떒寃궗 떊鍮숇룄議곗궗뒗 쟾泥댁쟻쑝濡 留ㅼ슦 슦닔븳 寃곌낵瑜 蹂댁떎[1-4]. BCR-ABL1, PML-RARA, AML1-ETO 옱諛곗뿴 臾명빆, JAK2, NPM1, KRAS, BRAF, EGFR, BRCA1, BRCA2, TP53, FGFR3, TGFBI, SCA1, SCA2, SCA3, SCA6, SCA7, MERRF, LHON PWS/AS, DMD, SMA, MTHFR genotyping쓽 빆紐⑹ 李몄뿬븳 紐⑤뱺 湲곌씠 1李⑥ 2李⑥뿉꽌 삁긽寃곌낵 씪移섑븳 寃곌낵瑜 蹂닿퀬븯떎.

寃궗踰붿쐞媛 븳젙맂 KIT瑜 궗슜븯뒗 湲곌뿉꽌뒗 寃궗遺쐞 씠쇅쓽 遺쐞뿉꽌룄 蹂씠瑜 寃異쒗븷 닔 엳뒗 븞쓣 留덈젴븯湲 沅뚯옣븳떎. 寃泥닿 諛붾뚯뼱 遺꾩꽍릺뿀떎怨 삁긽릺뒗 湲곌씠 엳뼱솕쑝誘濡 빐떦 湲곌뿉꽌뒗 留 쉶李⑤쭏떎 遺꾩꽍怨쇱젙쓣 諛섎뱶떆 솗씤빐빞 븳떎.

HGVS뿉꽌뒗 삤瑜섎 諛⑹븯뒗 李⑥썝뿉꽌 triple-letter amino acid code 궗슜쓣 沅뚯옣븯怨 엳쑝誘濡 紐⑤뱺 李몄뿬湲곌뱾뿉꽌뒗 protein level뿉꽌쓽 蹂씠뿉 빐 triple-letter amino acid code瑜 궗슜븳 寃곌낵엯젰쓣 沅뚯옣븯硫 듅엳 쑀쟾옄蹂씠 紐낅챸뿉꽌 옒紐삳맂 蹂씠遺쐞瑜 蹂닿퀬븯嫄곕굹 떒諛깆쭏蹂씠 삤湲곌 留롮씠 諛쒖깮븯誘濡 理쒖쥌蹂닿퀬 쟾 솗씤븷 닔 엳뒗 泥닿퀎瑜 援ъ꽦븯뒗 寃껋쓣 沅뚯옣븳떎.

룞씪 쑀쟾옄瑜 寃궗븯뒗 뿬윭 湲곌뿉꽌 媛곴린 떎瑜 reference transcript瑜 궗슜븯뒗 寃쎌슦媛 엳쑝誘濡 寃궗 떞떦옄뒗 二쇨린쟻쑝濡 reference transcript瑜 솗씤빐빞 븳떎. 蹂씠뿉 뵲瑜 빐꽍蹂닿퀬 遺꾩꽍븳 젙웾媛믪쑝濡 쑀쟾吏덊솚쓣 吏꾨떒븯뒗 寃쎌슦 蹂씠 빐꽍怨 젙웾媛믪쓽 湲곗씠 蹂븯뒗 寃쎌슦媛 醫낆쥌 엳쑝誘濡 愿젴 臾명뿄 諛 李멸퀬옄猷뚮 二쇨린쟻쑝濡 솗씤빐빞 븯硫 HGVS 諛 ACMG 愿젴 吏移⑥쓣 以닔븯뒗 寃껋쓣 沅뚯옣븳떎[5-7].

References
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