Format

Send to

Choose Destination
Sci Rep. 2019 Jun 21;9(1):9020. doi: 10.1038/s41598-019-45281-1.

NTHL1 biallelic mutations seldom cause colorectal cancer, serrated polyposis or a multi-tumor phenotype, in absence of colorectal adenomas.

Belhadj S1,2, Quintana I1,2, Mur P1,2,3, Munoz-Torres PM1,2, Alonso MH2,4,5,6, Navarro M1,2,3, Terradas M1,2, Piñol V7,8, Brunet J1,3,9, Moreno V2,4,5,6, Lázaro C1,2,3, Capellá G1,2,3, Valle L10,11,12.

Author information

1
Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Barcelona, Spain.
2
Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, 08908 Hospitalet de Llobregat, Barcelona, Spain.
3
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
4
Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology, IDIBELL, Barcelona, Spain.
5
Centro de Investigación Biomédica en Red de Epidemiologia y Salud Pública (CIBERESP), Madrid, Spain.
6
Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
7
Gastroenterology Unit, Hospital Universitario de Girona Dr Josep Trueta, 17007, Girona, Spain.
8
School of Medicine, University of Girona, 17071, Girona, Spain.
9
Hereditary Cancer Program, Catalan Institute of Oncology, IDIBGi, 17007, Girona, Spain.
10
Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Barcelona, Spain. lvalle@iconcologia.net.
11
Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, 08908 Hospitalet de Llobregat, Barcelona, Spain. lvalle@iconcologia.net.
12
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. lvalle@iconcologia.net.

Abstract

The cancer-predisposing syndrome caused by biallelic mutations in NTHL1 may not be a solely colorectal cancer (CRC) and polyposis syndrome but rather a multi-tumor recessive disease. The presence of ≤10 adenomas in several mutation carriers suggests a possible causal role of NTHL1 in hereditary or early-onset nonpolyposis CRC. The involvement of NTHL1 in serrated/hyperplastic polyposis remains unexplored. The aim of our study is to elucidate the role of NTHL1 in the predisposition to personal or familial history of multiple tumor types, familial/early-onset nonpolyposis CRC, and serrated polyposis. NTHL1 mutational screening was performed in 312 cancer patients with personal or family history of multiple tumor types, 488 with hereditary nonpolyposis CRC, and 96 with serrated/hyperplastic polyposis. While no biallelic mutation carriers were identified in patients with personal and/or family history of multiple tumor types or with serrated polyposis, one was identified among the 488 nonpolyposis CRC patients. The carrier of c.268C>T (p.Q90*) and 550-1G>A was diagnosed with CRC and meningioma at ages 37 and 45 respectively, being reclassified as attenuated adenomatous polyposis after the cumulative detection of 26 adenomas. Our findings suggest that biallelic mutations in NTHL1 rarely cause CRC, a personal/familial multi-tumor history, or serrated polyposis, in absence of adenomas.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center