Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair

Nuria Seguí; Leonardo B. Mina; Conxi Lázaro; Rebeca Sanz-Pamplona; Tirso Pons; Matilde Navarro; Fernando Bellido; Adriana López-Doriga; Rafael Valdés-Mas; Marta Pineda; Elisabet Guinó; August Vidal; José Luís Soto; Trinidad Caldés; Mercedes Durán; Miguel Urioste; Daniel Rueda; Joan Brunet; Milagros Balbín; Pilar Blay; Silvia Iglesias; Pilar Garré; Enrique Lastra; Ana Beatriz Sánchez-Heras; Alfonso Valencia; Victor Moreno; Miguel Ángel Pujana; Alberto Villanueva; Ignacio Blanco; Gabriel Capellá; Jordi Surrallés; Xose S. Puente; Laura Valle

doi:10.1053/j.gastro.2015.05.056

Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair

Nuria Seguí, Leonardo B. Mina, Conxi Lázaro, Rebeca Sanz-Pamplona, Tirso Pons, Matilde Navarro, Fernando Bellido, Adriana López-Doriga, Rafael Valdés-Mas, Marta Pineda, Elisabet Guinó, August Vidal, José Luís Soto, Trinidad Caldés, Mercedes Durán, Miguel Urioste, Daniel Rueda, Joan Brunet, Milagros Balbín, Pilar BlaySilvia Iglesias, Pilar Garré, Enrique Lastra, Ana Beatriz Sánchez-Heras, Alfonso Valencia, Victor Moreno, Miguel Ángel Pujana, Alberto Villanueva, Ignacio Blanco, Gabriel Capellá, Jordi Surrallés, Xose S. Puente, Laura Valle

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

Identification of genes associated with hereditary cancers facilitates management of patients with family histories of cancer. We performed exome sequencing of DNA from 3 individuals from a family with colorectal cancer who met the Amsterdam criteria for risk of hereditary nonpolyposis colorectal cancer. These individuals had mismatch repair-proficient tumors and each carried nonsense variant in the FANCD2/FANCI-associated nuclease 1 gene (FAN1), which encodes a nuclease involved in DNA inter-strand cross-link repair. We sequenced FAN1 in 176 additional families with histories of colorectal cancer and performed in vitro functional analyses of the mutant forms of FAN1 identified. We detected FAN1 mutations in approximately 3% of families who met the Amsterdam criteria and had mismatch repair-proficient cancers with no previously associated mutations. These findings link colorectal cancer predisposition to the Fanconi anemia DNA repair pathway, supporting the connection between genome integrity and cancer risk.

Original language	English
Pages (from-to)	563-566
Number of pages	4
Journal	Gastroenterology
Volume	149
Issue number	3
DOIs	https://doi.org/10.1053/j.gastro.2015.05.056
State	Published - 1 Sep 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 AGA Institute.

Keywords

DNA Mismatch Repair
Genetic Risk Factor
Lynch Syndrome
Susceptibility

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10.1053/j.gastro.2015.05.056

Cite this

Seguí, N., Mina, L. B., Lázaro, C., Sanz-Pamplona, R., Pons, T., Navarro, M., Bellido, F., López-Doriga, A., Valdés-Mas, R., Pineda, M., Guinó, E., Vidal, A., Soto, J. L., Caldés, T., Durán, M., Urioste, M., Rueda, D., Brunet, J., Balbín, M., ... Valle, L. (2015). Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair. Gastroenterology, 149(3), 563-566. https://doi.org/10.1053/j.gastro.2015.05.056

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title = "Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair",

abstract = "Identification of genes associated with hereditary cancers facilitates management of patients with family histories of cancer. We performed exome sequencing of DNA from 3 individuals from a family with colorectal cancer who met the Amsterdam criteria for risk of hereditary nonpolyposis colorectal cancer. These individuals had mismatch repair-proficient tumors and each carried nonsense variant in the FANCD2/FANCI-associated nuclease 1 gene (FAN1), which encodes a nuclease involved in DNA inter-strand cross-link repair. We sequenced FAN1 in 176 additional families with histories of colorectal cancer and performed in vitro functional analyses of the mutant forms of FAN1 identified. We detected FAN1 mutations in approximately 3% of families who met the Amsterdam criteria and had mismatch repair-proficient cancers with no previously associated mutations. These findings link colorectal cancer predisposition to the Fanconi anemia DNA repair pathway, supporting the connection between genome integrity and cancer risk.",

keywords = "DNA Mismatch Repair, Genetic Risk Factor, Lynch Syndrome, Susceptibility",

author = "Nuria Segu{\'i} and Mina, {Leonardo B.} and Conxi L{\'a}zaro and Rebeca Sanz-Pamplona and Tirso Pons and Matilde Navarro and Fernando Bellido and Adriana L{\'o}pez-Doriga and Rafael Vald{\'e}s-Mas and Marta Pineda and Elisabet Guin{\'o} and August Vidal and Soto, {Jos{\'e} Lu{\'i}s} and Trinidad Cald{\'e}s and Mercedes Dur{\'a}n and Miguel Urioste and Daniel Rueda and Joan Brunet and Milagros Balb{\'i}n and Pilar Blay and Silvia Iglesias and Pilar Garr{\'e} and Enrique Lastra and S{\'a}nchez-Heras, {Ana Beatriz} and Alfonso Valencia and Victor Moreno and Pujana, {Miguel {\'A}ngel} and Alberto Villanueva and Ignacio Blanco and Gabriel Capell{\'a} and Jordi Surrall{\'e}s and Puente, {Xose S.} and Laura Valle",

note = "Publisher Copyright: {\textcopyright} 2015 AGA Institute.",

year = "2015",

month = sep,

day = "1",

doi = "10.1053/j.gastro.2015.05.056",

language = "Ingl{\'e}s",

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Seguí, N, Mina, LB, Lázaro, C, Sanz-Pamplona, R, Pons, T, Navarro, M, Bellido, F, López-Doriga, A, Valdés-Mas, R, Pineda, M, Guinó, E, Vidal, A, Soto, JL, Caldés, T, Durán, M, Urioste, M, Rueda, D, Brunet, J, Balbín, M, Blay, P, Iglesias, S, Garré, P, Lastra, E, Sánchez-Heras, AB, Valencia, A, Moreno, V, Pujana, MÁ, Villanueva, A, Blanco, I, Capellá, G, Surrallés, J, Puente, XS & Valle, L 2015, 'Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair', Gastroenterology, vol. 149, no. 3, pp. 563-566. https://doi.org/10.1053/j.gastro.2015.05.056

TY - JOUR

T1 - Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair

AU - Seguí, Nuria

AU - Mina, Leonardo B.

AU - Lázaro, Conxi

AU - Sanz-Pamplona, Rebeca

AU - Pons, Tirso

AU - Navarro, Matilde

AU - Bellido, Fernando

AU - López-Doriga, Adriana

AU - Valdés-Mas, Rafael

AU - Pineda, Marta

AU - Guinó, Elisabet

AU - Vidal, August

AU - Soto, José Luís

AU - Caldés, Trinidad

AU - Durán, Mercedes

AU - Urioste, Miguel

AU - Rueda, Daniel

AU - Brunet, Joan

AU - Balbín, Milagros

AU - Blay, Pilar

AU - Iglesias, Silvia

AU - Garré, Pilar

AU - Lastra, Enrique

AU - Sánchez-Heras, Ana Beatriz

AU - Valencia, Alfonso

AU - Moreno, Victor

AU - Pujana, Miguel Ángel

AU - Villanueva, Alberto

AU - Blanco, Ignacio

AU - Capellá, Gabriel

AU - Surrallés, Jordi

AU - Puente, Xose S.

AU - Valle, Laura

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Identification of genes associated with hereditary cancers facilitates management of patients with family histories of cancer. We performed exome sequencing of DNA from 3 individuals from a family with colorectal cancer who met the Amsterdam criteria for risk of hereditary nonpolyposis colorectal cancer. These individuals had mismatch repair-proficient tumors and each carried nonsense variant in the FANCD2/FANCI-associated nuclease 1 gene (FAN1), which encodes a nuclease involved in DNA inter-strand cross-link repair. We sequenced FAN1 in 176 additional families with histories of colorectal cancer and performed in vitro functional analyses of the mutant forms of FAN1 identified. We detected FAN1 mutations in approximately 3% of families who met the Amsterdam criteria and had mismatch repair-proficient cancers with no previously associated mutations. These findings link colorectal cancer predisposition to the Fanconi anemia DNA repair pathway, supporting the connection between genome integrity and cancer risk.

AB - Identification of genes associated with hereditary cancers facilitates management of patients with family histories of cancer. We performed exome sequencing of DNA from 3 individuals from a family with colorectal cancer who met the Amsterdam criteria for risk of hereditary nonpolyposis colorectal cancer. These individuals had mismatch repair-proficient tumors and each carried nonsense variant in the FANCD2/FANCI-associated nuclease 1 gene (FAN1), which encodes a nuclease involved in DNA inter-strand cross-link repair. We sequenced FAN1 in 176 additional families with histories of colorectal cancer and performed in vitro functional analyses of the mutant forms of FAN1 identified. We detected FAN1 mutations in approximately 3% of families who met the Amsterdam criteria and had mismatch repair-proficient cancers with no previously associated mutations. These findings link colorectal cancer predisposition to the Fanconi anemia DNA repair pathway, supporting the connection between genome integrity and cancer risk.

KW - DNA Mismatch Repair

KW - Genetic Risk Factor

KW - Lynch Syndrome

KW - Susceptibility

UR - http://www.scopus.com/inward/record.url?scp=84938864161&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2015.05.056

DO - 10.1053/j.gastro.2015.05.056

M3 - Artículo

C2 - 26052075

AN - SCOPUS:84938864161

SN - 0016-5085

VL - 149

SP - 563

EP - 566

JO - Gastroenterology

JF - Gastroenterology

IS - 3

ER -

Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair

Abstract

Bibliographical note

Keywords

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