Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals.
Fam Cancer
; 10(4): 641-7, 2011 Dec.
Article
en En
| MEDLINE
| ID: mdl-21681552
ABSTRACT
Lynch syndrome (LS) is an autosomal dominant syndrome that predisposes individuals to development of cancers early in life. These cancers are mainly the following colorectal, endometrial, ovarian, small intestine, stomach and urinary tract cancers. LS is caused by germline mutations in DNA mismatch repair genes (MMR), mostly MLH1 and MSH2, which are responsible for more than 85% of known germline mutations. To search for germline mutations in MLH1 and MSH2 genes in 123 unrelated South American suspected LS patients (Bethesda or Amsterdam Criteria) DNA was obtained from peripheral blood, and PCR was performed followed by direct sequencing in both directions of all exons and intron-exon junctions regions of the MLH1 and MSH2 genes. MLH1 or MSH2 pathogenic mutations were found in 28.45% (34/123) of the individuals, where 25/57 (43.85%) fulfilled Amsterdam I, II and 9/66 (13.63%) the Bethesda criteria. The mutations found in both genes were as follows nonsense (35.3%), frameshift (26.47%), splicing (23.52%), and missense (9%). Thirteen alterations (35.14%) were described for the first time. The data reported in this study add new information about MLH1 and MSH2 gene mutations and contribute to better characterize LS in Brazil, Uruguay and Argentina. The high rate of novel mutations demonstrates the importance of defining MLH1 and MSH2 mutations in distinct LS populations.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Neoplasias Colorrectales Hereditarias sin Poliposis
/
Mutación de Línea Germinal
/
Proteínas Adaptadoras Transductoras de Señales
/
Proteína 2 Homóloga a MutS
/
Reparación de la Incompatibilidad de ADN
Límite:
Humans
País/Región como asunto:
America do sul
/
Argentina
/
Brasil
/
Uruguay
Idioma:
En
Revista:
Fam Cancer
Asunto de la revista:
NEOPLASIAS
Año:
2011
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS