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

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. Eleven LS hereditary cancer registrie...

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Published in:	BMC cancer Vol. 17; no. 1; p. 623
Main Authors:	Rossi, Benedito Mauro, Palmero, Edenir Inêz, López-Kostner, Francisco, Sarroca, Carlos, Vaccaro, Carlos Alberto, Spirandelli, Florencia, Ashton-Prolla, Patricia, Rodriguez, Yenni, de Campos Reis Galvão, Henrique, Reis, Rui Manuel, Escremim de Paula, André, Capochin Romagnolo, Luis Gustavo, Alvarez, Karin, Della Valle, Adriana, Neffa, Florencia, Kalfayan, Pablo German, Spirandelli, Enrique, Chialina, Sergio, Gutiérrez Angulo, Melva, Castro-Mujica, Maria Del Carmen, Sanchez de Monte, Julio, Quispe, Richard, da Silva, Sabrina Daniela, Rossi, Norma Teresa, Barletta-Carrillo, Claudia, Revollo, Susana, Taborga, Ximena, Morillas, L Lena, Tubeuf, Hélène, Monteiro-Santos, Erika Maria, Piñero, Tamara Alejandra, Dominguez-Barrera, Constantino, Wernhoff, Patrik, Martins, Alexandra, Hovig, Eivind, Møller, Pål, Dominguez-Valentin, Mev
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 05-09-2017 BioMed Central BMC
Subjects:	Adult Analysis Cancer Care and treatment Colorectal cancer Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis Colorectal Neoplasms, Hereditary Nonpolyposis - epidemiology Colorectal Neoplasms, Hereditary Nonpolyposis - genetics Computational Biology - methods Deoxyribonucleic acid DNA DNA Mismatch Repair Endometrial cancer Exons Family medical history Female Founder Effect Genes Genetic aspects Genetic Counseling Genetic disorders Genetic Predisposition to Disease Genetic screening Genetic Testing Genetic Variation Germ-Line Mutation Heredity Humans Immunohistochemistry Latin America Latin America - epidemiology Life Sciences Lynch syndrome Male Microsatellite instability Middle Aged Mismatch repair MLH1 protein Mmr MSH2 protein MSH6 protein Mutation Ovarian cancer Population Population Surveillance Practice Registries Risk Factors RNA Splicing Studies Surveys Tumors Variants Latin America South America Australia Mexico Variants Mmr Latin America Lynch syndrome
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Summary:	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. 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC5586063
ISSN:	1471-2407 1471-2407
DOI:	10.1186/s12885-017-3599-4