{"title":"Comparison of two cases of Familial Adenomatous Polyposis with the same APC genotype and different phenotypes","authors":"Eva Spier , Aashna Pandya , Miranda Di Biase","doi":"10.1016/j.cancergen.2024.10.008","DOIUrl":null,"url":null,"abstract":"<div><div>Familial adenomatous polyposis (FAP) is a colorectal cancer (CRC) predisposition syndrome characterized by the presence of numerous colorectal adenomatous polyps, resulting from a single germline, heterozygous, likely pathogenic/pathogenic (LP/P) variant in the <em>APC</em> gene, an important tumor suppressor encoding gene. Classic FAP is considered in individuals with a germline LP/P variant in <em>APC</em> and have ≥100 colorectal adenomatous polyps beginning on average in adolescence, while attenuated FAP typically presents with fewer colorectal adenomatous polyps (10-<100 polyps) in adulthood. Both forms can feature extracolonic manifestations, such as desmoid tumors, thyroid cancer, and osteomas. Reported genotype-phenotype correlations in FAP provide valuable insights for healthcare providers, but variable expressivity persists even among individuals sharing a genotype.</div><div>In this case study, we report two patients with the same pathogenic <em>APC</em> variant [c.4348C>T, p.Arg1450Ter] and different presentations and clinical findings. Case 1 describes a 21-year-old male with an extensive family history of cancer who was diagnosed with FAP at age 4. Case 2 describes a 22-year-old female with no family history who was diagnosed with FAP after she initially presented with a desmoid tumor. Despite genetic similarities, their clinical courses significantly differed, emphasizing the variable expressivity of FAP. These cases highlight the importance of individual management and surveillance, as genotype alone may not predict clinical outcomes. They also underscore the need for further research into factors that influence FAP expressivity.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 110-113"},"PeriodicalIF":1.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Genetics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2210776224001339","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Familial adenomatous polyposis (FAP) is a colorectal cancer (CRC) predisposition syndrome characterized by the presence of numerous colorectal adenomatous polyps, resulting from a single germline, heterozygous, likely pathogenic/pathogenic (LP/P) variant in the APC gene, an important tumor suppressor encoding gene. Classic FAP is considered in individuals with a germline LP/P variant in APC and have ≥100 colorectal adenomatous polyps beginning on average in adolescence, while attenuated FAP typically presents with fewer colorectal adenomatous polyps (10-<100 polyps) in adulthood. Both forms can feature extracolonic manifestations, such as desmoid tumors, thyroid cancer, and osteomas. Reported genotype-phenotype correlations in FAP provide valuable insights for healthcare providers, but variable expressivity persists even among individuals sharing a genotype.
In this case study, we report two patients with the same pathogenic APC variant [c.4348C>T, p.Arg1450Ter] and different presentations and clinical findings. Case 1 describes a 21-year-old male with an extensive family history of cancer who was diagnosed with FAP at age 4. Case 2 describes a 22-year-old female with no family history who was diagnosed with FAP after she initially presented with a desmoid tumor. Despite genetic similarities, their clinical courses significantly differed, emphasizing the variable expressivity of FAP. These cases highlight the importance of individual management and surveillance, as genotype alone may not predict clinical outcomes. They also underscore the need for further research into factors that influence FAP expressivity.
期刊介绍:
The aim of Cancer Genetics is to publish high quality scientific papers on the cellular, genetic and molecular aspects of cancer, including cancer predisposition and clinical diagnostic applications. Specific areas of interest include descriptions of new chromosomal, molecular or epigenetic alterations in benign and malignant diseases; novel laboratory approaches for identification and characterization of chromosomal rearrangements or genomic alterations in cancer cells; correlation of genetic changes with pathology and clinical presentation; and the molecular genetics of cancer predisposition. To reach a basic science and clinical multidisciplinary audience, we welcome original full-length articles, reviews, meeting summaries, brief reports, and letters to the editor.