Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population
Germline predisposition plays an important role in breast cancer. Different ethnic populations need respective studies on cancer risks pertinent to germline variants. We aimed to discover the pathogenic and likely pathogenic variants (P/LP-Vs) of germline breast cancer susceptibility genes and to ev...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/12/9/2241 |
| _version_ | 1797489424681926656 |
|---|---|
| author | Sonar Soni Panigoro Rafika Indah Paramita Kristina Maria Siswiandari Fadilah Fadilah |
| author_facet | Sonar Soni Panigoro Rafika Indah Paramita Kristina Maria Siswiandari Fadilah Fadilah |
| author_sort | Sonar Soni Panigoro |
| collection | DOAJ |
| description | Germline predisposition plays an important role in breast cancer. Different ethnic populations need respective studies on cancer risks pertinent to germline variants. We aimed to discover the pathogenic and likely pathogenic variants (P/LP-Vs) of germline breast cancer susceptibility genes and to evaluate their correlation with the clinical characteristics in Jakarta populations. The pure DNA was extracted from the blood buffy coat, using reagents from the QIAamp DNA Mini Kit<sup>®</sup> (Qiagen, Hilden, Germany). The DNA libraries were prepared using the TargetRich™ Hereditary Cancer Panel (Kailos Genetics<sup>®</sup>, Huntsville, AL, USA). The barcoded DNA libraries were sequenced using the Illumina NextSeq 500 platform. In-house bioinformatics pipelines were used to analyze the gene variants. We identified 35 pathogenic and likely pathogenic (P/LP-Vs) variants (28 frameshift, 5 nonsense, and 2 splice-site variants). The P/LP-Vs group was statistically significantly different in luminal B status (<i>p</i> < 0.05) compared with the non-P/LP-Vs group. The P/LP-Vs found both in BRCA1/2 genes and non-BRCA genes may increase the risk of breast cancer and alter drug responses. The screening of multigene variants is suggested, rather than BRCA testing only. Prior knowledge of the germline variants status is important for optimal breast cancer diagnosis and optimal therapy. |
| first_indexed | 2024-03-10T00:16:19Z |
| format | Article |
| id | doaj.art-ccae92086f87430087f105f696357e84 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T00:16:19Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-ccae92086f87430087f105f696357e842023-11-23T15:51:02ZengMDPI AGDiagnostics2075-44182022-09-01129224110.3390/diagnostics12092241Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta PopulationSonar Soni Panigoro0Rafika Indah Paramita1Kristina Maria Siswiandari2Fadilah Fadilah3Surgical Oncology Division, Department of Surgery, Faculty of Medicine, Universitas Indonesia, Central Jakarta 10430, DKI Jakarta, IndonesiaDoctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Central Jakarta 10430, DKI Jakarta, IndonesiaSurgical Oncology Division, Department of Surgery, Faculty of Medicine, Universitas Indonesia, Central Jakarta 10430, DKI Jakarta, IndonesiaDepartment of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Central Jakarta 10430, DKI Jakarta, IndonesiaGermline predisposition plays an important role in breast cancer. Different ethnic populations need respective studies on cancer risks pertinent to germline variants. We aimed to discover the pathogenic and likely pathogenic variants (P/LP-Vs) of germline breast cancer susceptibility genes and to evaluate their correlation with the clinical characteristics in Jakarta populations. The pure DNA was extracted from the blood buffy coat, using reagents from the QIAamp DNA Mini Kit<sup>®</sup> (Qiagen, Hilden, Germany). The DNA libraries were prepared using the TargetRich™ Hereditary Cancer Panel (Kailos Genetics<sup>®</sup>, Huntsville, AL, USA). The barcoded DNA libraries were sequenced using the Illumina NextSeq 500 platform. In-house bioinformatics pipelines were used to analyze the gene variants. We identified 35 pathogenic and likely pathogenic (P/LP-Vs) variants (28 frameshift, 5 nonsense, and 2 splice-site variants). The P/LP-Vs group was statistically significantly different in luminal B status (<i>p</i> < 0.05) compared with the non-P/LP-Vs group. The P/LP-Vs found both in BRCA1/2 genes and non-BRCA genes may increase the risk of breast cancer and alter drug responses. The screening of multigene variants is suggested, rather than BRCA testing only. Prior knowledge of the germline variants status is important for optimal breast cancer diagnosis and optimal therapy.https://www.mdpi.com/2075-4418/12/9/2241breast cancergermline variantsNGSsequencingyoung women |
| spellingShingle | Sonar Soni Panigoro Rafika Indah Paramita Kristina Maria Siswiandari Fadilah Fadilah Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population Diagnostics breast cancer germline variants NGS sequencing young women |
| title | Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population |
| title_full | Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population |
| title_fullStr | Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population |
| title_full_unstemmed | Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population |
| title_short | Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population |
| title_sort | targeted sequencing of germline breast cancer susceptibility genes for discovering pathogenic likely pathogenic variants in the jakarta population |
| topic | breast cancer germline variants NGS sequencing young women |
| url | https://www.mdpi.com/2075-4418/12/9/2241 |
| work_keys_str_mv | AT sonarsonipanigoro targetedsequencingofgermlinebreastcancersusceptibilitygenesfordiscoveringpathogeniclikelypathogenicvariantsinthejakartapopulation AT rafikaindahparamita targetedsequencingofgermlinebreastcancersusceptibilitygenesfordiscoveringpathogeniclikelypathogenicvariantsinthejakartapopulation AT kristinamariasiswiandari targetedsequencingofgermlinebreastcancersusceptibilitygenesfordiscoveringpathogeniclikelypathogenicvariantsinthejakartapopulation AT fadilahfadilah targetedsequencingofgermlinebreastcancersusceptibilitygenesfordiscoveringpathogeniclikelypathogenicvariantsinthejakartapopulation |