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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America

Authors: Benedito Mauro Rossi, Edenir Inêz Palmero, Francisco López-Kostner, Carlos Sarroca, Carlos Alberto Vaccaro, Florencia Spirandelli, Patricia Ashton-Prolla, Yenni Rodriguez, Henrique de Campos Reis Galvão, Rui Manuel Reis, André Escremim de Paula, Luis Gustavo Capochin Romagnolo, Karin Alvarez, Adriana Della Valle, Florencia Neffa, Pablo German Kalfayan, Enrique Spirandelli, Sergio Chialina, Melva Gutiérrez Angulo, Maria del Carmen Castro-Mujica, Julio Sanchez de Monte, Richard Quispe, Sabrina Daniela da Silva, Norma Teresa Rossi, Claudia Barletta-Carrillo, Susana Revollo, Ximena Taborga, L. Lena Morillas, Hélène Tubeuf, Erika Maria Monteiro-Santos, Tamara Alejandra Piñero, Constantino Dominguez-Barrera, Patrik Wernhoff, Alexandra Martins, Eivind Hovig, Pål Møller, Mev Dominguez-Valentin

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America.

Methods

Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome.

Results

We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet.

Conclusion

The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.
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Metadata
Title
A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America
Authors
Benedito Mauro Rossi
Edenir Inêz Palmero
Francisco López-Kostner
Carlos Sarroca
Carlos Alberto Vaccaro
Florencia Spirandelli
Patricia Ashton-Prolla
Yenni Rodriguez
Henrique de Campos Reis Galvão
Rui Manuel Reis
André Escremim de Paula
Luis Gustavo Capochin Romagnolo
Karin Alvarez
Adriana Della Valle
Florencia Neffa
Pablo German Kalfayan
Enrique Spirandelli
Sergio Chialina
Melva Gutiérrez Angulo
Maria del Carmen Castro-Mujica
Julio Sanchez de Monte
Richard Quispe
Sabrina Daniela da Silva
Norma Teresa Rossi
Claudia Barletta-Carrillo
Susana Revollo
Ximena Taborga
L. Lena Morillas
Hélène Tubeuf
Erika Maria Monteiro-Santos
Tamara Alejandra Piñero
Constantino Dominguez-Barrera
Patrik Wernhoff
Alexandra Martins
Eivind Hovig
Pål Møller
Mev Dominguez-Valentin
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3599-4

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