De novo familial adenomatous polyposis with germline double heterozygosity of APC/BRCA2: a case report and literature review.

IF 2 4区 医学 Q3 ONCOLOGY
Tian-Qi Zhang, Ji-Dong Cai, Cong Li, Yun Xu, Ye Xu
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引用次数: 0

Abstract

Background: The widespread application of colonoscopy screening and genetic testing in colorectal cancer (CRC) treatment has led to the identification of a subset of familial adenomatous polyposis (FAP) patients who lack a family history of the disease but harbor germline gene mutations. Moreover, distinct genotypes may be associated with varied clinical presentations and therapeutic options. This case report describes a male patient with de novo FAP who harbored germline double heterozygosity (GDH) for APC and BRCA2 mutations. The patient underwent total colectomy, and genetic testing enabled personalized surveillance and management strategies for his family members.

Case presentation: A 43-year-old male with no family history of cancer presented to the outpatient clinic of the Colorectal Surgery Department with complaints of constipation and hematochezia. Colonoscopy revealed hundreds of polyps throughout the colon and a rectal adenocarcinoma located 5 cm from the anal verge. Gastroduodenal endoscopy did not detect any upper gastrointestinal adenomas. The patient underwent laparoscopic total colectomy with abdominoperineal resection of the rectum and end ileostomy. With the consent of the patient and his family, genetic testing was performed. The index patient was found to carry an APC splicing site mutation (exon 15: c.1744-1G > A) and a BRCA2 missense mutation (exon 17: c.7976G > A: p.R2659K). His daughter was found to have inherited the same germline BRCA2 variant. Additionally, the rectal cancer exhibited proficient DNA mismatch repair (pMMR) status, ERBB2 copy number amplification, and a missense mutation, while the KRAS, NRAS, and BRAF genes were wild-type. Based on the genetic testing results and clinical manifestations, the index patient was diagnosed with familial adenomatous polyposis (FAP) and rectal cancer. Personalized surveillance and management strategies were implemented for the patient and his family, focusing on the risks of extra-colonic diseases and potential malignancies in the prostate, pancreas, breast, and ovaries.

Conclusion: De novo FAP with double germline mutations in APC and BRCA2, along with somatic ERBB2 mutations, is exceptionally rare among hereditary cancer cases. With the rapid advancements in genomics, the detection of multiple gene variants in individuals or families has become increasingly common. Additionally, the application of artificial intelligence (AI) in medical research may provide powerful tools for genetic analysis and clinical decision-making. Consequently, a comprehensive evaluation of family history, a deep understanding of hereditary cancer syndromes, and precise interpretation of genetic mutations are essential for personalized clinical management in the era of precision medicine. However, these tasks pose significant challenges for clinicians and genetic counselors alike.

新发家族性腺瘤性息肉病伴种系双杂合APC/BRCA2: 1例报告和文献复习。
背景:结肠镜筛查和基因检测在结直肠癌(CRC)治疗中的广泛应用,导致了家族性腺瘤性息肉病(FAP)患者的一个子集的鉴定,这些患者没有该疾病的家族史,但存在种系基因突变。此外,不同的基因型可能与不同的临床表现和治疗选择有关。本病例报告描述了一名患有新发FAP的男性患者,他携带APC和BRCA2突变的种系双杂合性(GDH)。患者接受了全结肠切除术,基因检测为其家庭成员提供了个性化的监测和管理策略。病例介绍:一名43岁男性,无癌症家族史,以便秘和便溺就诊于结直肠外科门诊。结肠镜检查发现数百个息肉遍布结肠,直肠腺癌位于距肛门边缘5厘米处。胃十二指肠镜未检出任何上消化道腺瘤。患者行腹腔镜全结肠切除术,腹会阴直肠切除术及回肠末端造口术。经患者及其家属同意,进行了基因检测。该患者被发现携带一个APC剪接位点突变(外显子15:c.1744-1G > A)和一个BRCA2错义突变(外显子17:c.7976G > A: p.R2659K)。他的女儿被发现遗传了相同的种系BRCA2变异。此外,直肠癌表现出熟练的DNA错配修复(pMMR)状态,ERBB2拷贝数扩增和错义突变,而KRAS, NRAS和BRAF基因为野生型。根据基因检测结果和临床表现,该患者被诊断为家族性腺瘤性息肉病(FAP)和直肠癌。对患者及其家属实施个性化监测和管理策略,重点关注结肠外疾病和前列腺、胰腺、乳房和卵巢潜在恶性肿瘤的风险。结论:APC和BRCA2双种系突变伴体细胞ERBB2突变的新生FAP在遗传性癌症病例中极为罕见。随着基因组学的快速发展,检测个体或家庭的多基因变异已经变得越来越普遍。此外,人工智能在医学研究中的应用可能为基因分析和临床决策提供强大的工具。因此,在精准医疗时代,全面评估家族史、深入了解遗传性癌症综合征以及精确解释基因突变对于个性化临床管理至关重要。然而,这些任务对临床医生和遗传咨询师都提出了重大挑战。
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来源期刊
CiteScore
3.10
自引率
5.90%
发文量
38
审稿时长
>12 weeks
期刊介绍: Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.
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