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Background: Lynch‐like syndrome (LLS) represents around 50% of the patients fulfilling the Amsterdam Criteria II/revised Bethesda Guidelines, characterized by a strong family history of Lynch Syndrome (LS) associated cancer, where a causative variant was not identified during genetic testing for LS.Methods: Using data extracted from a larger gene panel, we have analyzed next‐generation sequencing data from 22 mismatch repair (MMR) genes (MSH3, PMS1, MLH3, EXO1, POLD1, POLD3 RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, LIG1, RPA1, RPA2, RPA3, POLD2, POLD4, MLH1, MSH2, MSH6, and PMS2) in 274 LLS patients. Detected variants were annotated and filtered using ANNOVAR and FILTUS software.Results: Thirteen variants were revealed in MLH1, MSH2, and MSH6, all genes previously linked to LS. Five additional genes (EXO1, POLD1, RFC1, RPA1, and MLH3) were found to harbor 11 variants of unknown significance in our sample cohort, two of them being frameshift variants.Conclusion: We have shown that other genes associated with the process of DNA MMR have a high probability of being associated with LLS families. These findings indicate that the spectrum of genes that should be tested when considering an entity like Lynch‐like syndrome should be expanded so that a more inclusive definition of this entity can be developed. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. DOI: 10.1002/mgg3.850

Summary It is well established that micro-organisms colonize a variety of extreme environments, including habitats like oil reservoirs deep inside the earth crust. Here, we present the results of a comparative high-coverage DNA sequencing study of metagenomes derived from two different oil reservoirs, both located about 2.5 km subseafloor below the Norwegian Sea. A previously reported bioinformatic analysis of DNA sequence data derived from one of the reservoirs (Well I) indicated that the community is dominated by bacterial species with a smaller fraction of Archaea. Here, we report results of a similar analysis from another reservoir (Well II) located in the same geographical area, however, according to available geological knowledge lacking direct physical contact with Well I. Interestingly, the Well II community is largely dominated by Archaea with a subordinate fraction of Bacteria. Comparison of the two datasets showed that large fractions of the sequences are extremely similar, both with respect to identity (typically above 98%) and gene organization. We therefore conclude that both wells contain essentially the same organisms, but in different relative abundances. Assuming that the communities have been distinct for long timescales because of physical separation, the results also indicate that microbial growth in the reservoirs is extremely slow.

Microorganisms colonize a variety of extreme environments, and based on cultivation studies and analyses of PCR-amplified 16S rDNA sequences, microbial life appears to extend deep into the earth crust. However, none of these studies involved comprehensive characterizations of total DNA. Here we report results of a high-coverage DNA pyrosequencing of an apparently representative and uncontaminated sample from a deep sea oil reservoir located 2.5 km subsurface, attributing a pressure and temperature of 250 bars and 85°C respectively. Bioinformatic analyses of the DNA sequences indicate that the reservoir harbours a rich microbial community dominated by a smaller number of taxa. Comparison of the metagenome with sequences in databases indicated that there may have been contact between the oil reservoir and surface communities late in the sequence of geological events leading to oil reservoir formation. One specific gene, encoding a putative enolase, was synthesized and expressed in Escherichia coli. Enolase activity was confirmed and was found to be much more thermotolerant than for a corresponding E. coli enzyme, consistent with the conditions in the oil reservoir.