Double heterozygous pathogenic germline APC and MSH2 variants in a 16-year-old female diagnosed with colorectal cancer
8 affiliations
- 1Medical Oncology, Azienda Ospedaliero Universitaria Delle Marche, 60126 Ancona, Italy
- 2Medical Oncology, Marche Polytechnic University, 60126 Ancona, Italy
- 3Oncology Unit, “Santa Maria Della Misericordia” Hospital, 61029 Urbino, Italy
- 4Medical Oncology, Department of Clinical and Molecular Sciences, Marche Polytechnic University, 60126 Ancona, Italy
- 5Unit of Oncogenetics and Functional Oncogenomics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
- 6Anatomic Pathology Unit, University Hospital “Azienda Ospedaliero Universitario delle Marche”, 60126 Ancona, Italy
- 7Department of Biomedical Sciences and Public Health, Faculty of Medicine, Marche Polytechnic University, 60126 Ancona, Italy
- 8Pediatric Onco-Hematology Unit, Azienda Ospedaliero Universitaria Delle Marche, 60123 Ancona, Italy
Abstract
Germline pathogenic variants (PVs) of the APC gene cause familial adenomatous polyposis (FAP), whereas PVs in DNA mismatch repair (MMR) genes underlie Lynch Syndrome (LS), formerly known as hereditary non polyposis colorectal cancer (HNPCC). The coexistence of both hereditary syndromes in a single individual has been reported extremely rarely and only in a few patients, and the scant literature on this topic suggests an earlier onset and a more rapidly worsening form of colorectal cancer, compared with subjects who carry a single mutation. Here we describe a 16-year-old female who presented with multiple colonic polyps as well as an invasive colorectal carcinoma, and was found to harbor heterozygous pathogenic variants (PV) both in APC and MSH2 genes. Our patient also represents the unique reported case harboring both a MSH2-EPCAM large rearrangement in association with a frameshift APC PV. This case illustrates the unique clinical phenotype that can arise from simultaneous FAP and LS pathogenic mutations, highlights the importance of comprehensive genetic testing in young patients with aggressive disease and ultimately suggests a personalized follow-up and surveillance program in this case.
Related
- WITHDRAWN: Heterozygous germline MSH3 mutations, and probably MLH3 mutations, act as classical tumour suppressors, leading to excess somatic deletion mutations, signature ID4 and increased colorectal cancer risk
- A case of renal hypouricemia type 1 associated with compound heterozygous URAT1/SLC22A12 variants A209V and F379L: clinical evidence for their pathogenic significance
- Male breast cancer: clinicopathological features and prevalence of germline pathogenic variants
- A machine learning classifier reveals hidden rare biallelic heterozygous variants in the coding regions of Meniere disease genome
- Prevalence and Impact of a Pathogenic CYP27A1 Variant on the Phenotypes Among Patients with Monogenic Heterozygous Familial Hypercholesterolemia
BibTeX
@article{maccaroni2026double,
title = {{Double heterozygous pathogenic germline APC and MSH2 variants in a 16-year-old female diagnosed with colorectal cancer}},
author = {Elena Maccaroni and Riccardo Bacalini and Alessia Lancianese and Cecilia Copparoni and Riccardo Giampieri and Francesca Bianchi and Cristiana Brugiati and Laura Belvederesi and Elisa Ambrosini and Natalia Chiodi and Emma Nicol Serritelli and Giulia Ricci and Valentina Tarantino and Manuela Santarosa and Francesca Morgese and Alice Magnarini and Silvia Villani and Veronica Agostinelli and Giulia Mentrasti and Alessandra Mandolesi and Gaia Goteri and Paola Coccia and Rossana Berardi},
journal = {Familial Cancer},
year = {2026},
month = oct,
doi = {10.1007/s10689-026-00616-6},
url = {https://doi.org/10.1007/s10689-026-00616-6},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Double heterozygous pathogenic germline APC and MSH2 variants in a 16-year-old female diagnosed with colorectal cancer
AU - Elena Maccaroni
AU - Riccardo Bacalini
AU - Alessia Lancianese
AU - Cecilia Copparoni
AU - Riccardo Giampieri
AU - Francesca Bianchi
AU - Cristiana Brugiati
AU - Laura Belvederesi
AU - Elisa Ambrosini
AU - Natalia Chiodi
AU - Emma Nicol Serritelli
AU - Giulia Ricci
AU - Valentina Tarantino
AU - Manuela Santarosa
AU - Francesca Morgese
AU - Alice Magnarini
AU - Silvia Villani
AU - Veronica Agostinelli
AU - Giulia Mentrasti
AU - Alessandra Mandolesi
AU - Gaia Goteri
AU - Paola Coccia
AU - Rossana Berardi
PY - 2026
DA - 2026/10/29
JO - Familial Cancer
DO - 10.1007/s10689-026-00616-6
UR - https://doi.org/10.1007/s10689-026-00616-6
AB - Germline pathogenic variants (PVs) of the APC gene cause familial adenomatous polyposis (FAP), whereas PVs in DNA mismatch repair (MMR) genes underlie Lynch Syndrome (LS), formerly known as hereditary non polyposis colorectal cancer (HNPCC). The coexistence of both hereditary syndromes in a single individual has been reported extremely rarely and only in a few patients, and the scant literature on this topic suggests an earlier onset and a more rapidly worsening form of colorectal cancer, compared with subjects who carry a single mutation. Here we describe a 16-year-old female who presented with multiple colonic polyps as well as an invasive colorectal carcinoma, and was found to harbor heterozygous pathogenic variants (PV) both in APC and MSH2 genes. Our patient also represents the unique reported case harboring both a MSH2-EPCAM large rearrangement in association with a frameshift APC PV. This case illustrates the unique clinical phenotype that can arise from simultaneous FAP and LS pathogenic mutations, highlights the importance of comprehensive genetic testing in young patients with aggressive disease and ultimately suggests a personalized follow-up and surveillance program in this case.
SN - 1389-9600
SN - 1573-7292
ER -