Contribution of large genomic rearrangements in Italian Lynch syndrome patients: characterization of a novel Alu-mediated deletion

Giuseppe Diana, Bianca Maria Cudia, Angela Cavallo, Raffaella Liccardo, Marina De Rosa, Francesca Duraturo, Paola Izzo

Risultato della ricerca: Article

17 Citazioni (Scopus)

Abstract

Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Mostof the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangementsin the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied onaverage from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenicpoint mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6in one of the patients analysed (1.6% frequency). This deletion was confirmed and localised by long-range PCR. The breakpointsof this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement wasa product of Alu-mediated recombination. Our fndings identified a novel Alu-mediated rearrangement within MSH2 gene andshowed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italianpatients with an inherited predisposition to colon cancer.
Lingua originaleEnglish
Numero di pagine0
RivistaDefault journal
Volume2013
Stato di pubblicazionePublished - 2013

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Hereditary Nonpolyposis Colorectal Neoplasms
Genes
DNA Mismatch Repair
Repair
Mutation
Germ-Line Mutation
Point Mutation
Gene Frequency
Colonic Neoplasms
Genetic Recombination
Exons
Polymerase Chain Reaction
DNA
Population

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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Contribution of large genomic rearrangements in Italian Lynch syndrome patients: characterization of a novel Alu-mediated deletion. / Diana, Giuseppe; Cudia, Bianca Maria; Cavallo, Angela; Liccardo, Raffaella; De Rosa, Marina; Duraturo, Francesca; Izzo, Paola.

In: Default journal, Vol. 2013, 2013.

Risultato della ricerca: Article

Diana, Giuseppe ; Cudia, Bianca Maria ; Cavallo, Angela ; Liccardo, Raffaella ; De Rosa, Marina ; Duraturo, Francesca ; Izzo, Paola. / Contribution of large genomic rearrangements in Italian Lynch syndrome patients: characterization of a novel Alu-mediated deletion. In: Default journal. 2013 ; Vol. 2013.
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abstract = "Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Mostof the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangementsin the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied onaverage from 5 to 20{\%}. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenicpoint mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6in one of the patients analysed (1.6{\%} frequency). This deletion was confirmed and localised by long-range PCR. The breakpointsof this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement wasa product of Alu-mediated recombination. Our fndings identified a novel Alu-mediated rearrangement within MSH2 gene andshowed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italianpatients with an inherited predisposition to colon cancer.",
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T1 - Contribution of large genomic rearrangements in Italian Lynch syndrome patients: characterization of a novel Alu-mediated deletion

AU - Diana, Giuseppe

AU - Cudia, Bianca Maria

AU - Cavallo, Angela

AU - Liccardo, Raffaella

AU - De Rosa, Marina

AU - Duraturo, Francesca

AU - Izzo, Paola

PY - 2013

Y1 - 2013

N2 - Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Mostof the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangementsin the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied onaverage from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenicpoint mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6in one of the patients analysed (1.6% frequency). This deletion was confirmed and localised by long-range PCR. The breakpointsof this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement wasa product of Alu-mediated recombination. Our fndings identified a novel Alu-mediated rearrangement within MSH2 gene andshowed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italianpatients with an inherited predisposition to colon cancer.

AB - Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Mostof the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangementsin the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied onaverage from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenicpoint mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6in one of the patients analysed (1.6% frequency). This deletion was confirmed and localised by long-range PCR. The breakpointsof this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement wasa product of Alu-mediated recombination. Our fndings identified a novel Alu-mediated rearrangement within MSH2 gene andshowed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italianpatients with an inherited predisposition to colon cancer.

UR - http://hdl.handle.net/10447/98613

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VL - 2013

JO - Default journal

JF - Default journal

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