Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

<p>Abstract</p> <p>Background</p> <p>Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (<it>MMR</it>) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from <it>MLH1</it>/<it>MSH2 </it>deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts.</p> <p>Methods</p> <p>The main <it>MMR </it>genes responsible for HNPCC, <it>MLH1</it>, <it>MSH2</it>, <it>MSH6</it>, and <it>PMS2</it>, were analyzed by MLPA (multiplex ligation-dependent probe amplification) in a total of 37 unrelated HNPCC-suspected patients whose <it>MLH1/MSH2 </it>genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the <it>MLH1 </it>and <it>MSH2 </it>genes.</p> <p>Results</p> <p>We found six rearrangements in the <it>MSH2 </it>gene (five deletions and dup5-6), and one aberration in the <it>MLH1 </it>gene (del5-6). The <it>MSH2 </it>deletions were of three types (del1, del1-3, del1-7). We detected LOH at the LGR region in the single <it>MLH1 </it>case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region.</p> <p>Conclusion</p> <p>LGRs accounted for 25% of germline <it>MMR </it>mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the <it>MSH2 </it>mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the <it>MLH1 </it>or <it>MSH2 </it>gene (heterozygous LGR region, SNP, or microsatellite) is a novel finding and can be regarded as a partial LOH. The conversion begins within the gene, and the details of conversion tracts are discussed for each case.</p

Description of Pseudoinsalebria Slamka, Ylla & Macià, gen. n. and Pseudoinsalebria iberica Slamka, Ylla & Macià, sp. n., a closely related species to Pseudoinsalebria albipunctella (Chrétien, 1911) (Lepidoptera: Pyralidae, Phycitinae)

A new genus of Phycitinae - Pseudoinsalebria Slamka, Ylla & Macià, gen. nov. and a new species - Pseudoinsalebria iberica Slamka, Ylla & Macià sp. nov. are described from the south of Spain. The genus Pseudoinsalebria differs from the related genera Insalebria Filipjev, 1924 and Selagia Hübner, [1825] 1816 by external characters and also by male and female genitalia. Pseudoinsalebria iberica differs from the closely related P. albipunctella (Chrétien, 1911) by the forewing markings and by male and female genitalia. Photographs of the adults and figures of the genitalia of both species are provided. KEY WORDS: Lepidoptera, Pyralidae, Phycitinae, Pseudoinsalebria, new genus, Pseudoinsalebria iberica, new species, Spain

Description of Pseudoinsalebria Slamka, Ylla & Macià, gen. n. and Pseudoinsalebria iberica Slamka, Ylla & Macià, sp. n., a closely related species to Pseudoinsalebria albipunctella (Chrétien, 1911) (Lepidoptera: Pyralidae, Phycitinae)

A new genus of Phycitinae - Pseudoinsalebria Slamka, Ylla & Macià, gen. nov. and a new species - Pseudoinsalebria iberica Slamka, Ylla & Macià sp. nov. are described from the south of Spain. The genus Pseudoinsalebria differs from the related genera Insalebria Filipjev, 1924 and Selagia Hübner, [1825] 1816 by external characters and also by male and female genitalia. Pseudoinsalebria iberica differs from the closely related P. albipunctella (Chrétien, 1911) by the forewing markings and by male and female genitalia. Photographs of the adults and figures of the genitalia of both species are provided. KEY WORDS: Lepidoptera, Pyralidae, Phycitinae, Pseudoinsalebria, new genus, Pseudoinsalebria iberica, new species, Spain.A new genus of Phycitinae - Pseudoinsalebria Slamka, Ylla & Macià, gen. nov. and a new species - Pseudoinsalebria iberica Slamka, Ylla & Macià sp. nov. are described from the south of Spain. The genus Pseudoinsalebria differs from the related genera Insalebria Filipjev, 1924 and Selagia Hübner, [1825] 1816 by external characters and also by male and female genitalia. Pseudoinsalebria iberica differs from the closely related P. albipunctella (Chrétien, 1911) by the forewing markings and by male and female genitalia. Photographs of the adults and figures of the genitalia of both species are provided. KEY WORDS: Lepidoptera, Pyralidae, Phycitinae, Pseudoinsalebria, new genus, Pseudoinsalebria iberica, new species, Spain.A new genus of Phycitinae - Pseudoinsalebria Slamka, Ylla & Macià, gen. nov. and a new species - Pseudoinsalebria iberica Slamka, Ylla & Macià sp. nov. are described from the south of Spain. The genus Pseudoinsalebria differs from the related genera Insalebria Filipjev, 1924 and Selagia Hübner, [1825] 1816 by external characters and also by male and female genitalia. Pseudoinsalebria iberica differs from the closely related P. albipunctella (Chrétien, 1911) by the forewing markings and by male and female genitalia. Photographs of the adults and figures of the genitalia of both species are provided. KEY WORDS: Lepidoptera, Pyralidae, Phycitinae, Pseudoinsalebria, new genus, Pseudoinsalebria iberica, new species, Spain