Abstract 3438: DNA methylation profiles of Helicobacter pylori strains from patients with gastric cancer and gastritis

Abstract BACKGROUND: Helicobacter pylori, a gram-negative bacterium associated with a spectrum of benign and malignant gastric conditions, is one of the most genetically variable pathogens. Its genome encodes a large number of DNA methyltransferases targeting specific motif sequences of ∼4-15 bp. DN...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.3438-3438
Main Authors: Camargo, M. Constanza, Torres, Javier, Solnick, Jay V., Raley, Castle, Storey, Dylan, Becker, Marina, Torres, Roberto, Weis, Allison, Huang, Carol, Kong, Nguyet, Hanson, Lori M., Zhao, Yongmei, Chen, Xiongfong, Tran, Bao, Weimer, Bart, Rabkin, Charles S.
Format: Article
Language:English
Subjects:
Helicobacter pylori
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Summary:Abstract BACKGROUND: Helicobacter pylori, a gram-negative bacterium associated with a spectrum of benign and malignant gastric conditions, is one of the most genetically variable pathogens. Its genome encodes a large number of DNA methyltransferases targeting specific motif sequences of ∼4-15 bp. DNA base modifications epigenetically regulate gene expression and genome-wide methylation profiles (methylomes) have been hypothesized to be associated with virulence. A limited number of H. pylori methylomes have been published to date, precluding meaningful analyses of clinical correlates. METHODS: We sequenced 30 H. pylori clinical isolates from Mexico City using Pacific Biosciences’ Single Molecule Real-Time (SMRT) technology, a unique platform that simultaneously determines a wide range of DNA base modifications. The resulting methylome data were compared for the 15 strains from gastric cancer cases vs. the 15 from non-atrophic gastritis controls. RESULTS: All 30 strains exhibited high levels of DNA methylation throughout their genomes. Three types of base modification were detected: N6-methyladenine (m6A), N4-methylcytosine (m4C) and 5-methylcytosine (m5C). m6A was more common than m4C, and m5C was rare. Over 100 different motifs were detected, including many novel motifs not found in the three reference strains. For most methylated motifs, >95% of all occurrences in a given genome were methylated. Individual strains had between 14 and 28 different motifs. Some of the methylated motifs were conserved across all (e.g., Cm6ATG) or almost all (e.g., Gm6ACT) strains, but the majority were found in only one or two strains. Two conserved motifs, GTm6AC and GTNNm6AC, were significantly (P
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2016-3438