Merete Rasmussen

Roskilde University, Roskilde, Zealand, Denmark

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Publications (4)12.66 Total impact

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    ABSTRACT: Somatic defects in the mismatch repair system constitute an important pathway in colorectal carcinogenesis. We have examined the expression of mismatch repair proteins in sporadic stage IV colorectal tumors and their derived metastases. Sporadic tumors were further examined for differences in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined. Clinicopathological parameters and Ki-67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant difference in the proliferative index was observed for the hMLH1/hPMS2-compromised group. In stage IV tumors re-expression of hMLH1/hPMS2 occurred, leading to different patterns of expression within the primary tumor and between tumor and metastases. This may have functional importance for the chemosensitivity of metastases compared to the primary tumor.
    Apmis 11/2009; 117(11):839-48. · 2.07 Impact Factor
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    ABSTRACT: The definition of a hypothetical protein is a protein that is predicted to be expressed from an open reading frame, but for which there is no experimental evidence of translation. Hypothetical proteins constitute a substantial fraction of proteomes of human as well as of other eukaryotes. With the general belief that the majority of hypothetical proteins are the product of pseudogenes, it is essential to have a tool with the ability of pinpointing the minority of hypothetical proteins with a high probability of being expressed. Here, we present an in silico selection strategy where eukaryotic hypothetical proteins are sorted according to two criteria that can be reliably identified in silico: the presence of subcellular targeting signals and presence of characterized protein domains. To validate the selection strategy we applied it on a database of human hypothetical proteins dating to 2006 and compared the proteins predicted to be expressed by our selecting strategy, with their status in 2008. For the comparison we focused on mitochondrial proteins, since considerable amounts of research have focused on this field in between 2006 and 2008. Therefore, many proteins, defined as hypothetical in 2006, have later been characterized as mitochondrial. Among the total amount of human proteins hypothetical in 2006, 21% have later been experimentally characterized and 6% of those have been shown to have a role in a mitochondrial context. In contrast, among the selected hypothetical proteins from the 2006 dataset, predicted by our strategy to have a mitochondrial role, 53-62% have later been experimentally characterized, and 85% of these have actually been assigned a role in mitochondria by 2008.Therefore our in silico selection strategy can be used to select the most promising candidates for subsequent in vitro and in vivo analyses.
    BMC Bioinformatics 09/2009; 10:289. · 3.02 Impact Factor
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    ABSTRACT: So far 18 MLH3 germline mutations/variants have been identified in familial colorectal cancer cases. Sixteen of these variants are amino acid substitutions of which the pathogenic nature is still unclear. These substitutions are known as unclassified variants or UVs. To clarify a possible role for eight of these MLH3 UVs identified in suspected Lynch syndrome patients, we performed several biochemical tests. We determined the protein expression and stability, protein localization and interaction of the mutant MLH3 proteins with wildtype MLH1. All eight MLH3 UVs gave protein expression levels comparable with wildtype MLH3. Furthermore, the UV-containing proteins, in contrast to previous studies, were all localized normally in the nucleus and they interacted normally with wildtype MLH1. Our different biochemical assays yielded no evidence that the eight MLH3 UVs tested are the cause of hereditary colorectal cancer, including Lynch syndrome.
    Genes Chromosomes and Cancer 02/2009; 48(4):340-50. · 3.55 Impact Factor
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    ABSTRACT: Mitochondrial DNA (mtDNA) alterations are implicated in a broad range of human diseases and alterations of the mitochondrial genome are assumed to be a result of its high susceptibility to oxidative damage and its limited DNA repair compared to nuclear DNA (nDNA). Characterization of DNA repair mechanisms has generally focused on these processes in nDNA but increasing interest and research effort have contributed to our knowledge of the mechanisms underlying DNA repair in mitochondria. In this review, we make comparisons between nDNA and mtDNA repair pathways and propose a model for how these pathways interact in mitochondria.
    Mitochondrion 05/2005; 5(2):89-108. · 4.03 Impact Factor