AccScience Publishing / CP / Online First / DOI: 10.36922/cp.5394
Submit to CP
Cite this article
3
Download
48
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
CASE REPORT

A new germline mutation in BRCA1 in a Chinese family with gynecologic cancers and colon cancer mimicking ovarian cancer: A case report

Bao Chai1 ,  Ya-Rong Guo2* ,  Zhi-Yong Shi3 ,  Yang Liu4
Show Less
1 Department of Gastroenterology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
2 Department of Digestive System Oncology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
3 Department of Surgery, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
4 The Third Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
CP, 5394 https://doi.org/10.36922/cp.5394
Received: 22 October 2024 | Revised: 5 February 2025 | Accepted: 7 April 2025 | Published online: 28 November 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
XML
Cite
Abstract

BRCA1 is a key player in the homologous recombination DNA repair process. Pathogenic BRCA1 germline mutations confer a high risk of breast and ovarian cancers. Nevertheless, the association between BRCA1 mutations and colorectal cancer (CRC) risk remains unclear. While BRCA1 alterations significantly influence diagnosis and therapeutic decisions in breast and ovarian cancer, including the use of FDA-approved poly (ADP-ribose) polymerase (PARP) inhibitors, their role in CRC management is less established. Here, we present a case of a 57-year-old female diagnosed with CRC and a family history of ovarian and endometrial cancers. All her cancer-affected family members, including herself, were found to carry two germline BRCA1 mutations, including a novel mutation (c.212+2T>G) that has not previously been reported in CRC. The proband exhibited peculiar clinicopathological and molecular features, including a CK7-positive/CK20-negative immunophenotype that mimicked an ovarian origin. The patient received five cycles of nab-paclitaxel plus carboplatin, followed by maintenance therapy with the PARP inhibitor (PARPi) niraparib. This case provides real-world evidence supporting the pathogenicity of the BRCA1 c.212+2T>G mutation and highlights the potential of PARPi therapy in CRC patients harboring BRCA1 mutations. Further, it demonstrates the possibility of a rare immunohistochemical phenotype in CRC cells harboring a deleterious BRCA1 mutation.

Keywords
BRCA1 germline mutation
Colorectal cancer
Rare immunophenotype
Family history
Funding
This work was supported by the China Postdoctoral Science Foundation (2021M702051), Shanxi Province Foundation for Returnees (20210004), and the Central Guidance on Local Science and Technology Foundation (YDZJSX2021A041).
Conflict of interest
Linhan Li was a previous employee of Genetron Health Co., Ltd., Beijing, China. However, the author has not influenced the content of the manuscript. No reference to the author’s company is made, but it is declared for full transparency. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
References
  1. Masood A, Hudhud KH, Hegazi AZ, Gupta NC. BRCA1 mutation presenting with primary breast colon cancer. Am J Case Rep. 2008;9:338-341.

 

  1. Soyano AE, Baldeo C, Kasi PM. BRCA mutation and its association with colorectal cancer. Clin Colorectal Cancer. 2018;17(4):e647-e650. doi: 10.1016/j.clcc.2018.06.006

 

  1. Gurioli G, Tedaldi G, Farolfi A, et al. Clinical impact of next-generation sequencing multi-gene panel highlighting the landscape of germline alterations in ovarian cancer patients. Int J Mol Sci. 2022;23(24):15789. doi: 10.3390/ijms232415789

 

  1. Calo V, Agnese V, Gargano G, et al. A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer. Breast Cancer Res Treat. 2006;96(1):97-100. doi: 10.1007/s10549-005-9049-z

 

  1. Celik E, Ermis Tekkus K, Akcay IM, et al. Identification of a BRCA2 mutation in a Turkish family with early-onset breast cancer. Clin Case Rep. 2018;6(9):1751-1755. doi: 10.1002/ccr3.1625

 

  1. Cullinane CM, Creavin B, O’Connell EP, et al. Risk of colorectal cancer associated with BRCA1 and/or BRCA2 mutation carriers: Systematic review and meta-analysis. Br J Surg. 2020;107(8):951-959. doi: 10.1002/bjs.11603

 

  1. Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021;134(7):783-791. doi: 10.1097/CM9.0000000000001474

 

  1. Lee MS, Kopetz S. Are homologous recombination deficiency mutations relevant in colorectal cancer? J Natl Cancer Inst. 2022;114(2):176-178. doi: 10.1093/jnci/djab170

 

  1. Ali M, Delozier CD, Chaudhary U. BRIP-1 germline mutation and its role in colon cancer: Presentation of two case reports and review of literature. BMC Med Genet. 2019;20(1):75. doi: 10.1186/s12881-019-0812-0

 

  1. Sopik V, Phelan C, Cybulski C, Narod SA. BRCA1 and BRCA2 mutations and the risk for colorectal cancer. Clin Genet. 2015;87(5):411-8. doi: 10.1111/cge.12497

 

  1. Maccaroni E, Giampieri R, Lenci E, et al. BRCA mutations and gastrointestinal cancers: When to expect the unexpected? World J Clin Oncol. 2021;12(7):565-580. doi: 10.5306/wjco.v12.i7.565

 

  1. Vietri MT, Caliendo G, D’Elia G, et al. Five Italian families with two mutations in BRCA genes. Genes (Basel). 2020;11(12):1451. doi: 10.3390/genes11121451

 

  1. Gao X, Nan X, Liu Y, et al. Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients. Hum Mutat. 2020;41(3):696-708. doi: 10.1002/humu.23965

 

  1. Van Thuan T, Van Chu N, Khoa PH, et al. A novel BRCA1 gene mutation detected with breast cancer in a vietnamese family by targeted next-generation sequencing: A case report. Breast Cancer (Auckl). 2020;14:1178223420901555. doi: 10.1177/1178223420901555

 

  1. Molinaro E, Andrikou K, Casadei-Gardini A, Rovesti G. BRCA in gastrointestinal cancers: Current treatments and future perspectives. Cancers (Basel). 2020;12(11):3346. doi: 10.3390/cancers12113346

 

  1. Grinshpun A, Halpern N, Granit RZ, et al. Phenotypic characteristics of colorectal cancer in BRCA1/2 mutation carriers. Eur J Hum Genet. 2018;26(3):382-386. doi: 10.1038/s41431-017-0067-1

 

  1. Phelan CM, Iqbal J, Lynch HT, et al. Incidence of colorectal cancer in BRCA1 and BRCA2 mutation carriers: Results from a follow-up study. Br J Cancer. 2014;110(2):530-534. doi: 10.1038/bjc.2013.741

 

  1. Zikan M, Vecerova L, Dubova O, Sehnal B, Soukupova J. BRCA mutation carriers suffering from ovarian cancer as a model for treatment decision in higher lines - Place for platinum reinduction. J Cancer Res Ther. 2023;19(3): 684-687. doi: 10.4103/jcrt.jcrt_880_21

 

  1. Conteduca V, Scarpi E, Farolfi A, et al. Melphalan as a promising treatment for BRCA-related ovarian carcinoma. Front Oncol. 2021;11:716467. doi: 10.3389/fonc.2021.716467

 

  1. Helleday T. The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing up the misunderstandings. Mol Oncol. 2011;5(4):387-393. doi: 10.1016/j.molonc.2011.07.001

 

  1. Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer. 2004;4(9):665-676. doi: 10.1038/nrc1431

 

  1. Nacson J, Di Marcantonio D, Wang Y, et al. BRCA1 mutational complementation induces synthetic viability. Mol Cell. 2020;78(5):951-959.e6. doi: 10.1016/j.molcel.2020.04.006

 

  1. Nykamp K, Anderson M, Powers M, et al. Sherloc: A comprehensive refinement of the ACMG-AMP variant classification criteria. Genet Med. 2017;19(10):1105-1117. doi: 10.1038/gim.2017.37

 

  1. Carraro DM, Koike Folgueira MA, Garcia Lisboa BC, et al. Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: A portrait of early-onset breast cancer in Brazil. PLoS One. 2013;8(3):e57581. doi: 10.1371/journal.pone.0057581

 

  1. Findlay GM, Daza RM, Martin B, et al. Accurate classification of BRCA1 variants with saturation genome editing. Nature. 2018;562(7726):217-222. doi: 10.1038/s41586-018-0461-z

 

  1. Houdayer C, Caux-Moncoutier V, Krieger S, et al. Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. Hum Mutat. 2012;33(8):1228-1238. doi: 10.1002/humu.22101

 

  1. Bhaskaran SP, Chandratre K, Gupta H, et al. Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. Int J Cancer. 2019;145(4):962-973. doi: 10.1002/ijc.32176

 

  1. Oh M, McBride A, Yun S, et al. BRCA1 and BRCA2 gene mutations and colorectal cancer risk: Systematic review and meta-analysis. J Natl Cancer Inst. 2018;110(11):1178-1189. doi: 10.1093/jnci/djy148

 

  1. Cullinane C, Brett A, Devane L, McCullough PW, Cooke F, Neary P. The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: A systematic review and meta-analysis. Colorectal Dis. 2023;25(10):1949-1959. doi: 10.1111/codi.16724

 

  1. Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Speizer FE, Willett WC. A prospective study of family history and the risk of colorectal cancer. N Engl J Med. 1994;331(25): 1669-1674. doi: 10.1056/NEJM199412223312501

 

  1. Lee SY, Shin A, Kim BC, et al. Association between family history of malignant neoplasm with colorectal adenomatous polyp in 40s aged relative person. Cancer Epidemiol. 2014;38(5):623-627. doi: 10.1016/j.canep.2014.06.005

 

  1. Huang W, Bian J, Qian X, et al. Case report: Coinheritance of germline mutations in APC and BRCA1 in colorectal cancer. Front Oncol. 2021;11:658389. doi: 10.3389/fonc.2021.658389

 

  1. Park JH, Jung DH, Baek JH. Metastatic colon cancer of an ovarian cancer origin mimicking primary colon cancer: A case report. Korean J Clin Oncol. 2018;14(1):53-57. doi: 10.14216/kjco.18009

 

  1. Xu Y, Li C, Wang Z, Liu F, Xu Y. Comparison of suspected Lynch syndrome patients carrying BRCA and BRCA-like variants with Lynch syndrome probands: Phenotypic characteristics and pedigree analyses. Mol Genet Genomic Med. 2020;8(8):e1359. doi: 10.1002/mgg3.1359

 

  1. Santandrea G, Piana S, Valli R, et al. Immunohistochemical biomarkers as a surrogate of molecular analysis in ovarian carcinomas: A review of the literature. Diagnostics (Basel). 2021;11(2):199. doi: 10.3390/diagnostics11020199

 

  1. Kolling S, Ventre F, Geuna E, et al. Metastatic cancer of unknown primary or primary metastatic cancer? Front Oncol. 2019;9:1546. doi: 10.3389/fonc.2019.01546

 

  1. Bayrak R, Haltas H, Yenidunya S. The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: Cytokeratin 7-/20+ phenotype is more specific than CDX2 antibody. Diagn Pathol. 2012;7:9. doi: 10.1186/1746-1596-7-9

 

  1. Bayrak R, Yenidunya S, Haltas H. Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas. Pathol Res Pract. 2011;207(3):156-160. doi: 10.1016/j.prp.2010.12.005

 

  1. Shin JH, Bae JH, Lee A, et al. CK7, CK20, CDX2 and MUC2 Immunohistochemical staining used to distinguish metastatic colorectal carcinoma involving ovary from primary ovarian mucinous adenocarcinoma. Jpn J Clin Oncol. 2010;40(3):208-213. doi: 10.1093/jjco/hyp150

 

  1. Aldaoud N, Erashdi M, AlKhatib S, Abdo N, Al-Mohtaseb A, Graboski-Bauer A. The utility of PAX8 and SATB2 immunohistochemical stains in distinguishing ovarian mucinous neoplasms from colonic and appendiceal mucinous neoplasm. BMC Res Notes. 2019;12(1):770. doi: 10.1186/s13104-019-4816-9

 

  1. Luo C, Cen S, Ding G, Wu W. Mucinous colorectal adenocarcinoma: Clinical pathology and treatment options. Cancer Commun (Lond). 2019;39(1):13. doi: 10.1186/s40880-019-0361-0

 

  1. Fei F, Li C, Cao Y, et al. CK7 expression associates with the location, differentiation, lymph node metastasis, and the Dukes’ stage of primary colorectal cancers. J Cancer. 2019;10(11):2510-2519. doi: 10.7150/jca.29397

 

  1. Remo A, Fassan M, Vanoli A, et al. Morphology and molecular features of rare colorectal carcinoma histotypes. Cancers (Basel). 2019;11(7):1036. doi: 10.3390/cancers11071036

 

  1. Wittersheim M, Buttner R, Markiefka B. Genotype/ Phenotype correlations in patients with hereditary breast cancer. Breast Care (Basel). 2015;10(1):22-26. doi: 10.1159/000380900

 

  1. de Jonge MM, Ritterhouse LL, de Kroon CD, et al. Germline BRCA-associated endometrial carcinoma is a distinct clinicopathologic entity. Clin Cancer Res. 2019;25(24): 7517-7526. doi: 10.1158/1078-0432.CCR-19-0848

 

  1. Harpaz N, Gatt YE, Granit RZ, Fruchtman H, Hubert A, Grinshpun A. Mucinous histology, BRCA1/2 mutations, and elevated tumor mutational burden in colorectal cancer. J Oncol. 2020;2020:6421205. doi: 10.1155/2020/6421205

 

  1. Herold N, Wappenschmidt B, Markiefka B, et al. Non-small cell neuroendocrine carcinoma of the ovary in a BRCA2-germline mutation carrier: A case report and brief review of the literature. Oncol Lett. 2018;15(4): 4093-4096. doi: 10.3892/ol.2018.7836

 

  1. Pimenta JR, Ueda SKN, Peixoto RD. Excellent response to olaparib in a patient with metastatic pancreatic adenocarcinoma with germline BRCA1 mutation after progression on FOLFIRINOX: Case report and literature review. Case Rep Oncol. 2020;13(2):904-910. doi: 10.1159/000508533

 

  1. Gorbunova V, Beck JT, Hofheinz RD, et al. A phase 2 randomised study of veliparib plus FOLFIRI±bevacizumab versus placebo plus FOLFIRI±bevacizumab in metastatic colorectal cancer. Br J Cancer. 2019;120(2):183-189. doi: 10.1038/s41416-018-0343-z

 

  1. Pishvaian MJ, Slack RS, Jiang W, et al. A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients with heavily pretreated metastatic colorectal cancer. Cancer. 2018;124(11):2337-2346. doi: 10.1002/cncr.31309

 

  1. Arena S, Corti G, Durinikova E, et al. A subset of colorectal cancers with cross-sensitivity to olaparib and oxaliplatin. Clin Cancer Res. 2020;26(6):1372-1384. doi: 10.1158/1078-0432.CCR-19-2409

 

  1. Mauri G, Arena S, Siena S, Bardelli A, Sartore-Bianchi A. The DNA damage response pathway as a land of therapeutic opportunities for colorectal cancer. Ann Oncol. 2020;31(9):1135-1147. doi: 10.1016/j.annonc.2020.05.027
Next article in this issue
Share
Back to top
Cancer Plus, Electronic ISSN: 2661-3840 Print ISSN: 2661-3832, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept