Sergio Alonso

Publications (15) View all

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  Available from: Sergio Alonso

  Article: Draft Genome Sequence of the Steroid Degrader Rhodococcus ruber Strain Chol-4

  Laura Fernández de las Heras, Sergio Alonso, Antonio de la Vega de León, Daniela Xavier, Julián Perera, Juana María Navarro Llorens
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  ABSTRACT: The whole-genome shotgun sequence of Rhodococcus ruber strain Chol-4 is presented here. This organism was shown to be able to grow using many steroids as the sole carbon and energy sources. These sequence data will help us to further explore the metabolic abilities of this versatile degrader.
  Genome Announcements. 05/2013; 1(3):e00215-13.
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  Available from: Sergio Alonso

  Article: Array-based identification of common DNA methylation alterations in ulcerative colitis.

  Kei Koizumi, Sergio Alonso, Yuichiro Miyaki, Shinichiro Okada, Hiroyuki Ogura, Norihiko Shiiya, Fumio Konishi, Toshiki Taya, Manuel Perucho, Koichi Suzuki
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  ABSTRACT: Patients with long-standing ulcerative colitis (UC) have higher risk of developing colorectal cancer. Albeit the causes remain to be understood, epigenetic alterations have been suggested to play a role in the long-term cancer risk of these patients. In this work, we developed a novel microarray platform based on methylation-sensitive amplified fragment length polymorphism (MS-AFLP) DNA fingerprinting. The over 10,000 NotI sites of the human genome were used to generate synthetic primers covering these loci that are equally distributed into CpG rich regions (promoters and CpG islands) and outside the CpG islands, providing a panoramic view of the methylation alterations in the genome. The arrays were first tested using the colon cancer cell line CW-2 showing the reproducibility and sensitivity of the approach. We next investigated DNA methylation alterations in the colonic mucosa of 14 UC patients. We identified epigenetic alterations affecting genes putatively involved in UC disease, and in susceptibility to develop colorectal cancer. There was a strong concordance of methylation alterations (both hypermethylation and hypomethylation) shared by the cancer cells of the CW-2 cell line and the non-cancer UC samples. To the best of our knowledge, this work defines the first high-throughput aberrant DNA methylation profiles of the colonic mucosa of UC patients. These epigenetic profiles provide novel and relevant knowledge on the molecular alterations associated to the UC pathology. Some of the detected alterations could be exploited as cancer risk predictors underlying a field defect for cancerization in UC-associated carcinogenesis.
  International Journal of Oncology 12/2011; 40(4):983-94. · 2.40 Impact Factor
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  Article: Frequent somatic demethylation of RAPGEF1/C3G intronic sequences in gastrointestinal and gynecological cancer.

  Johanna Samuelsson, Sergio Alonso, Tatiana Ruiz-Larroya, Tak Hong Cheung, Yick Fu Wong, Manuel Perucho
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  ABSTRACT: RAPGEF1 (also known as C3G and GRF2) is a guanine nucleotide exchange factor that releases GDP from the inactive Rap1 protein, facilitating its subsequent activation by the binding of GTP. Rap1 plays regulatory roles in proliferation, differentiation and apoptosis. Amplification and overexpression of RAPGEF1 have been found in small cell lung cancers, suggesting an oncogenic role. In contrast, hypermethylation of a promoter CpG island (CGI-A) of RAPGEF1 has been reported in squamous cervical tumors, suggesting an anti-oncogenic role in these gynecological cancers. In our studies of DNA methylation alterations in gastrointestinal cancer we found somatic demethylation of a relaxed-criterion CpG island (CGI-B) located in the first intron of RAPGEF1 in 40% of colon cancers and 8% of gastric cancers relative to their matching normal tissues that were always methylated. We also found somatic demethylation in 47% of squamous cervical carcinomas as well as 33% of ovarian cancers. This somatic change in methylation, however, did not extend to the strict-criterion CpG island located in the promoter region (CGI-A) that was unmethylated in all normal and tumor tissues analyzed. Thus, promoter hypermethylation of RAPGEF1 seems insignificant in colorectal, cervical and ovarian cancers. In contrast, tumor-specific hypomethylation of the gene appears to be frequent in gastrointestinal and gynecological cancers.
  International Journal of Oncology 03/2011; 38(6):1575-7. · 2.40 Impact Factor
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  Article: DNA fingerprinting techniques for the analysis of genetic and epigenetic alterations in colorectal cancer.

  Johanna K Samuelsson, Sergio Alonso, Fumiichiro Yamamoto, Manuel Perucho
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  ABSTRACT: Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in carcinogenesis. Epigenetic regulation mechanisms underlie the maintenance of cell identity crucial for development and differentiation. These epigenetic regulatory mechanisms have been found substantially altered during cancer development and progression. In this review, we discuss approaches designed to analyze genetic and epigenetic alterations in colorectal cancer, especially DNA fingerprinting approaches to detect changes in DNA copy number and methylation. DNA fingerprinting techniques, despite their modest throughput, played a pivotal role in significant discoveries in the molecular basis of colorectal cancer. The aim of this review is to revisit the fingerprinting technologies employed and the oncogenic processes that they unveiled.
  Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 11/2010; 693(1-2):61-76. · 2.85 Impact Factor
• Article: Down-regulation of epidermal growth factor receptor by selective expansion of a 5'-end regulatory dinucleotide repeat in colon cancer with microsatellite instability.

  Svetlana Baranovskaya, Yolanda Martin, Sergio Alonso, Ksenia L Pisarchuk, Mario Falchetti, Yuichi Dai, Sophia Khaldoyanidi, Stan Krajewski, Inna Novikova, Yuri S Sidorenko, Manuel Perucho, Sergei R Malkhosyan
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  ABSTRACT: The epidermal growth factor receptor (EGFR) is overexpressed in several tumor types, and its expression is influenced by the length of a 5'-end microsatellite repeat (CA)n: the longer the repeat, the lower the expression. Dinucleotide repeats accumulate insertion/deletion types of mutations in tumors with microsatellite instability. We designed this study to estimate the occurrence of these mutations in EGFR(CA)n and their relevance in carcinogenesis of microsatellite instability-positive colon and gastric tumors. We analyzed the frequency of EGFR(CA)n mutations in vivo in 55 colorectal and 14 gastric microsatellite instability-positive cancers, and in vitro in single-cell clone cultures of microsatellite instability-positive colon tumor cell line LS174. Single-cell clone cultures with different repeat lengths were analyzed by fluorescent-activated cell sorter for EGFR cell-surface expression. A correlation analysis was done between EGFR(CA)n mutations and mutations in KRAS, BRAF, and p53. Unlike single-cell clone cultures, which exhibited higher rate of deletions compared with insertions, most of EGFR(CA)n mutations in colon and gastric tumors were insertions. Longer EGFR(CA)n correlated with lower EGFR cell-surface expression in single-cell clone cultures. In colon cancers, the elongation of the repeat was associated negatively with mutations in KRAS and BRAF, but not in p53. The EGFR(CA)n elongation observed in tumors cannot be explained by an intrinsic property of this repeat favoring insertions versus deletions. Instead, a selection for repeat elongation occurs in microsatellite instability-positive tumors, leading to EGFR down-regulation. These findings suggest that in microsatellite instability-positive tumors current therapies targeting EGFR overexpression may have either no effect or an opposite to the expected effect.
  Clinical Cancer Research 08/2009; 15(14):4531-7. · 7.74 Impact Factor