RESUMO
Hereditary nonpolyposis colorectal cancer is an autosomal dominant cancer predisposition syndrome caused by inherited germ line mutations in DNA mismatch repair genes, predominantly MSH2 and MLH1. Here we report the first proven de novo germ line mutation in MLH1 (c.666dupA) identified in a 31-year-old colorectal cancer patient with the alteration being present in a heterozygous state in all three germ layers and homozygously in his colon cancer. The mutation was absent in both biological parents and all sibs available. Despite extensive polymorphic marker analysis, the parental origin of c.666dupA could not be conclusively determined, representing either a single mutational event in a parental germ cell or (maternal) gonadal mosaicism. Although rare, consequential application of the Bethesda guidelines for genetic testing should allow the clinician to readily identify colorectal cancer patients below age 50 years who carry de novo mismatch repair gene mutations.
Assuntos
Adenocarcinoma/genética , Proteínas de Transporte/genética , Neoplasias Colorretais/genética , Mutação em Linhagem Germinativa , Proteínas Nucleares/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutLRESUMO
The t(2;18)(p12;q21), known as a rare variant of the t(14;18)(q32;q21), together with t(3;14)(q27;q32), t(8;15)(q24;q22) and two other unusual translocations involving chromosomes 6, 9, 12, and 13, were demonstrated in the bone marrow cells of a 70-year-old male with suspected non-Hodgkin lymphoma/acute lymphoblastic leukemia. The complex chromosomal aberrations were identified by chromosome banding analysis and by fluorescence in situ hybridization (FISH) with whole chromosome painting probes, centromere-specific alpha-satellite probes, and probes specific for genomic sequences of some likely to be involved candidate genes. Several but not all of the chromosomal aberrations could be proved by multicolor FISH. Possible mechanisms leading to this unusual karyotype commonly associated with different histologic lymphoma subtypes and their prognostic implications are discussed.
