Cancer Research and Treatment

Original Articles

Prevalence and Potential Clinical Relevance of Germline Pathogenic Variants in Korean Biliary Tract Cancer: Jun-Ha Jang, Jong Eun Park, Jung Won Chun, Hyeji Kim, Jinhyuk Bhin, Junghyeok Lim, Sang Myung Woo, Joo Kyung Park, Dae Wook Hwang, Sung-Sik Han, Woo Jin Lee, Dong-Eun Lee, Sang-Jae Park, Sun-Young Kong; Received April 30, 2026 Accepted July 20, 2026 Published online July 21, 2026; DOI: https://doi.org/10.4143/crt.2026.0484 [Accepted]

Abstract PDF: Purpose
This study aimed to identify germline pathogenic/likely pathogenic variants in DNA damage repair genes associated with increased cancer risk in Korean patients with biliary tract cancer and characterize their population-specific patterns.
Materials and Methods
In this retrospective multicenter cohort study, we performed germline whole-exome sequencing in 172 Korean patients diagnosed with intrahepatic cholangiocarcinoma (n = 83) or gallbladder cancer (n = 89) between June 2001 and February 2022. Germline variants were analyzed in 210 hereditary cancer genes, and the germline landscape of this cohort was compared with that of global cohorts.
Results
Pathogenic/likely pathogenic variants were identified in 24 of 172 (14.0%) patients, predominantly in DNA damage repair genes (18 of 24 [75.0%]). BRCA2 was among the most frequently altered genes, harboring two distinct pathogenic variants (2 of 24 [8.3%]; both cases of intrahepatic cholangiocarcinoma). Of the 24 carriers, five (20.8%) harbored Tier 1–2 variants of potential, tumor-confirmation-dependent therapeutic relevance. Notably, 15 of 24 (62.5%) carriers reported no family cancer history. In population-stratified comparisons across nine biliary tract cancer cohorts (n = 4,018), PMS2 showed a Korean-enriched signal after accounting for heterogeneous gene coverage, whereas TP53 showed only a directional, non-significant increase after multiple-testing correction.
Conclusion
The study findings provide reference data for genetic counseling in East Asian patients with biliary tract cancer and suggest that germline testing may warrant consideration regardless of family history.

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Gastrointestinal cancer

Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer: Seung-Young Oh, Giyong Jang, Jaeryuk Kim, Kyoung-Yun Jeong, Hyun Myong Kim, Yoon Jin Kwak, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Sung-Yup Cho, Jong-Il Kim, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1126-1135. Published online April 11, 2024; DOI: https://doi.org/10.4143/crt.2024.328

Purpose
Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression.
Materials and Methods
Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation, and enrichment analysis were performed.
Results
As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in-silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the Rhoa^R129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked Rhoa^R129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families.
Conclusion
The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

Citations

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Association of C5AR1 polymorphisms with increased gastric cancer risk: mechanistic insights and therapeutic implications targeting JAK/STAT pathway
Zhongqi Wang, Ying Jian, Xiaomei Jiang, Hongmei Zhang, Zhi Zhang, Xuemei Zhang
Gene.2026; 991: 150086. CrossRef
Hereditary diffuse gastric cancer: the evolution of a cancer syndrome
Lyvianne Decourtye‐Espiard, Tanis Godwin, Parry Guilford
Journal of the Royal Society of New Zealand.2025; 55(6): 2636. CrossRef
A Comprehensive Review of Genetic Mutations Occurring in the Development and Progression of Gastric Cancer
Yalan Li, Qianqian Xu, Zhuo Chen, Mengting Chen, Kunyu Han, Zhuqing Zhang, Aling Shen, Xiaoyan Fu
Digestive Diseases.2025; 43(6): 630. CrossRef
Helicobacter pylori infection status and evolution of gastric cancer
Wenlin Zhang, Yuxin Zhang, Jing Ning, Weiwei Fu, Shigang Ding
Chinese Medical Journal.2025; 138(23): 3083. CrossRef
Current advances and challenges in Managing Hereditary Diffuse Gastric Cancer (HDGC): a narrative review
L. van der Sluis, J.M. van Dieren, R.S. van der Post, T.M. Bisseling
Hereditary Cancer in Clinical Practice.2024;[Epub] CrossRef

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Breast cancer

Short-term Impact of Hormone Replacement Therapy on Risk of Breast Cancer in BRCA Mutation Carriers: A Nationwide Study in South Korea: Hye Yeon Kim, Jisoo Park, Seok Joo Moon, Sohyeon Jeong, Jin Hwa Hong, Jae Kwan Lee, Geum Joon Cho, Hyun-Woong Cho; Cancer Res Treat. 2024;56(1):143-148. Published online August 16, 2023; DOI: https://doi.org/10.4143/crt.2023.653

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Purpose
BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO.
Materials and Methods
A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups.
Results
There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278).
Conclusion
In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO.

Citations

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Menopausal hormone treatment and breast cancer
Anne Gompel, Richard Simcock
The Lancet Diabetes & Endocrinology.2026; 14(3): 259. CrossRef
Risiko endokriner Interventionen bei Trägerinnen einer genetischen Disposition für Brustkrebs und gynäkologische Krebserkrankungen
Susanne Schüler-Toprak, Karin Kast, Olaf Ortmann, T. Fehm, A. Hahne, D. Huber, K. Kast, E. Kühnle, K. Mohr, O. Ortmann, K. Rhiem, S. Schüler-Toprak, S. Seitz, D. Speiser
Gynäkologische Endokrinologie.2026; 24(2): 74. CrossRef
Hormone Therapy After Oophorectomy and Breast Cancer Risk in Women With BRCA Pathogenic Variant
Shira Regev-Sadeh, Rachel Michaelson-Cohen, Dana Madorksy-Feldman, Eitan Friedman, Shunit Armon, Amalfi Qarawani, Naama Srebnik, Joul Haddad, Vered H. Eisenberg, Yakir Segev
JAMA Network Open.2026; 9(4): e265648. CrossRef
Epidemiology, Genetic Etiology, and Intervention of Premature Ovarian Insufficiency
Ting Guo, Hongyuan Liu, Bingying Xu, Yu Qi, Keyan Xu, Xinyi Wu, Xinmiao He, Yingying Qin, Zi-Jiang Chen
Endocrine Reviews.2025; 46(5): 621. CrossRef
Cancer du sein chez la femme en âge de procréer : problématiques autour du rôle des hormones
Ondine Dufour, Andréa Villeneuve, Blandine Courbiere, Alexandre de Nonneville
Bulletin du Cancer.2025; 112(7-8): 867. CrossRef
A contemporary review of breast cancer risk factors and the role of artificial intelligence
Orietta Nicolis, Denisse De Los Angeles, Carla Taramasco
Frontiers in Oncology.2024;[Epub] CrossRef

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Rare cancer

Clinical Features of Li-Fraumeni Syndrome in Korea: Ran Song, Sun-Young Kong, Wonyoung Choi, Eun-Gyeong Lee, Jaeyeon Woo, Jai Hong Han, Seeyoun Lee, Han-Sung Kang, So-Youn Jung; Cancer Res Treat. 2024;56(1):334-341. Published online August 9, 2023; DOI: https://doi.org/10.4143/crt.2023.794

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Purpose
Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS.
Materials and Methods
Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected.
Results
Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively.
Conclusion
This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

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Association of DNA damage response pathway genes with rheumatoid arthritis risks: a case-control study
Muhammad Zahid Hussain, Muhammad Haris Khan, Muhammad Shahbaz Haris, Rida Huzaira, Ammarah Munawar, Maria Fazal Ul Haq, Rabia Shafique, Ishrat Mahjabeen
Scientific Reports.2025;[Epub] CrossRef
Description of six cases of melanoma in 512 patients with germline pathogenic variants in the TP53 gene
Elisabeth de A. C. Callegaro, Janina Pontes Pisani, Vanessa Monteleone, Maria Isabel Achatz
Familial Cancer.2025;[Epub] CrossRef
Consensus Statement: Recommendations on Actionable Biomarker Testing for Thyroid Cancer Management
Ozgur Mete, Andrée Boucher, Kasmintan A. Schrader, Omar Abdel-Rahman, Houda Bahig, Cheryl Ho, Olfat Kamel Hasan, Bernard Lemieux, Eric Winquist, Ralph Wong, Jonn Wu, Nicole Chau, Shereen Ezzat
Endocrine Pathology.2024; 35(4): 293. CrossRef

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Breast cancer

Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation: Ju Won Kim, Hyo Eun Kang, Jimi Choi, Seung Gyu Yun, Seung Pil Jung, Soo Yeon Bae, Ji Young You, Yoon-Ji Choi, Yeul Hong Kim, Kyong Hwa Park; Cancer Res Treat. 2023;55(1):155-166. Published online June 8, 2022; DOI: https://doi.org/10.4143/crt.2021.1567

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Purpose
BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants.
Materials and Methods
Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity.
Results
A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w.
Conclusion
We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

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Clinico-Pathological Factors Determining Recurrence of Phyllodes Tumors of the Breast: The 25-Year Experience at a Tertiary Cancer Centre
Baijaeek Sain, Arnab Gupta, Aruni Ghose, Sudip Halder, Vishal Mukherjee, Samir Bhattacharya, Radha Raman Mondal, Aditya Narayan Sen, Bijan Saha, Shravasti Roy, Stergios Boussios
Journal of Personalized Medicine.2023; 13(5): 866. CrossRef

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Prevalence of PALB2 Germline Mutations in Early-onset and Familial Breast/Ovarian Cancer Patients from Pakistan: Muhammad Usman Rashid, Faiz Ali Khan, Noor Muhammad, Asif Loya, Ute Hamann; Cancer Res Treat. 2019;51(3):992-1000. Published online October 11, 2018; DOI: https://doi.org/10.4143/crt.2018.356

Abstract PDF PubReader ePub

Purpose
Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan.
Materials and Methods
PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations.
Results
A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127, 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5' untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (≤ 30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated.
Conclusion
Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.

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Mahboubeh Sadeghi, Abbas Ghaderi, Pegah Mousavi, Soudabeh Sabetian, Amin Ramezani, Mohammad Reza Haghshenas
Medical Oncology.2026;[Epub] CrossRef
Anticipation effect in Pakistani breast cancer families with or without BRCA1/2 pathogenic variants
Noor Muhammad, Humaira Naeemi, Shumaila Arif, Ute Hamann, Muhammad Usman Rashid
Cancer Epidemiology.2025; 96: 102782. CrossRef
Genetic landscape of Pakistani familial breast cancer patients using multigene panel testing
Muhammad Usman Rashid, Noor Muhammad, Shumaila Arif, Humaira Naeemi, Ute Hamann
International Journal of Cancer.2025; 157(10): 2081. CrossRef
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Kalyani R. Thombre, Krishna Radheshyam Gupta, Milind Janrao Umekar
Current Pharmacogenomics and Personalized Medicine.2025;[Epub] CrossRef
Prevalence of FANCM germline variants in BRCA1/2 negative breast and/or ovarian cancer patients from Pakistan
Muhammad Usman Rashid, Noor Muhammad, Umara Shehzad, Faiz Ali Khan, Asif Loya, Ute Hamann
Familial Cancer.2023; 22(1): 31. CrossRef
Potential prognostic role of somatic mutations in a set of cancer susceptibility genes in ovarian carcinoma: A follow-up multicentric study from Pakistan
Atika Masood, Rahat Sarfaraz, Saima Zaki, Amira Shami, Saba Khaliq, Nadia Naseem
Cancer Biomarkers.2023; 36(3): 207. CrossRef
Contribution of constitutional BRCA1 promoter methylation to early-onset and familial breast cancer patients from Pakistan
Noor Muhammad, Ayesha Azeem, Muhammad Abu Bakar, Karolina Prajzendanc, Asif Loya, Anna Jakubowska, Ute Hamann, Muhammad Usman Rashid
Breast Cancer Research and Treatment.2023; 202(2): 377. CrossRef
Low prevalence of germline TP53 and PALB2 mutations in unselected cohort of breast cancer patients from Brunei Darussalam
Siti Nur Idayu Matusin, Zen Huat Lu, Mas Rina Wati Haji Abdul Hamid
F1000Research.2023; 12: 1537. CrossRef
Germline Mutation Analysis in Sporadic Breast Cancer Cases With Clinical Correlations
Sadia Ajaz, Sani-e-Zehra Zaidi, Saleema Ali, Aisha Siddiqa, Muhammad Ali Memon
Frontiers in Genetics.2022;[Epub] CrossRef
Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan
Fizza Akbar, Zahraa Siddiqui, Muhammad Talha Waheed, Lubaina Ehsan, Syed Ibaad Ali, Hajra Wiquar, Azmina Tajuddin Valimohammed, Shaista Khan, Lubna Vohra, Sana Zeeshan, Yasmin Rashid, Munira Moosajee, Adnan Abdul Jabbar, Muhammad Nauman Zahir, Naila Zahid
Hereditary Cancer in Clinical Practice.2022;[Epub] CrossRef
Contribution of germline PALB2 variants to an unselected and prospectively registered pancreatic cancer patient cohort in Pakistan
Noor Muhammad, Rida Sadaqat, Humaira Naeemi, Iqra Masood, Usman Hassan, Bushra Ijaz, Faisal Hanif, Aamir A. Syed, Muhammed A. Yusuf, Muhammad U. Rashid
HPB.2022; 24(12): 2134. CrossRef
Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients
Muhammad Usman Rashid, Noor Muhammad, Faiz Ali Khan, Umara Shehzad, Humaira Naeemi, Naila Malkani, Ute Hamann
Hereditary Cancer in Clinical Practice.2020;[Epub] CrossRef

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Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review: Byung Su Kwon, Jung Mi Byun, Hyun Joo Lee, Dae Hoon Jeong, Tae Hwa Lee, Kyung-Hwa Shin, Dong Soo Suh, Ki Hyung Kim; Cancer Res Treat. 2019;51(3):941-950. Published online October 8, 2018; DOI: https://doi.org/10.4143/crt.2018.312

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients.
Materials and Methods
Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review.
Results
Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (p<0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2 mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2 mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC).
Conclusion
The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.

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Family Caring, Culture, and Communication: Barriers to BRCA-Related Risk Disclosure in Korea—A Qualitative Study
Juhye Jin, Jeehee Han, Soo Yeon Kim, Maria C. Katapodi, Sue Kim
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BRCA Testing in Asian Patients with Ovarian Cancer: Standard Clinical Practice or Mutation Prediction Model?
Boon Hong Ang, Sook-Yee Yoon, Joanna Lim, Nur Tiara Hassan, Mei-Chee Tai, Zhi Lei Wong, Jo Yi Chow, Xin Wen Lee, Meow-Keong Thong, Gaik-Siew Ch’ng, Jamil Omar, Chee-Meng Yong, Ismail Aliyas, Rozita Abdul Malik, Suguna Subramaniam, Wee-Wee Sim, Chun Sen Li
Cancer Epidemiology, Biomarkers & Prevention.2026; 35(7): 1129. CrossRef
Prevalence of BRCA1 and BRCA2 mutations in ovarian cancer patients from Yunnan Province in southwest China
Yongmei Peng, Jiaqian Liao, Xian He, Yongchun Zhou, Lei Zhang, Yue Jia, Hongying Yang
European Journal of Cancer Prevention.2025; 34(3): 231. CrossRef
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Yeungnam University Journal of Medicine.2020; 37(3): 179. CrossRef

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Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2: Kyung Jin Eoh, Ji Eun Kim, Hyung Seok Park, Seung-Tae Lee, Ji Soo Park, Jung Woo Han, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Jae Hoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2018;50(3):917-925. Published online September 27, 2017; DOI: https://doi.org/10.4143/crt.2017.220

Abstract PDF Supplementary Material PubReader ePub

Purpose
Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS.
Materials and Methods
Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing.
Results
Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance.
Conclusion
Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

Citations

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Prevalence of germline CHEK2 variants in East Asians and Koreans based on population genomic databases
Jong Eun Park, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Jung-Sook Ha, Do Hoon Kim, Kyoung-Bo Kim, Chang-Seok Ki, Sun-Young Kong
Breast Cancer.2026; 33(1): 80. CrossRef
Pathogenic germline variants among patients with ovarian cancer by self-reported ancestry: A commercial laboratory collaborative research registry study
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Journal of Medical Genetics.2018; 55(9): 571. CrossRef

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