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Somatic Mutations throughout the Entire Mitochondrial Genome Are Associated with Elevated PSA Levels in Prostate Cancer Patients  Anita Kloss-Brandstätter,

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Presentation on theme: "Somatic Mutations throughout the Entire Mitochondrial Genome Are Associated with Elevated PSA Levels in Prostate Cancer Patients  Anita Kloss-Brandstätter,"— Presentation transcript:

1 Somatic Mutations throughout the Entire Mitochondrial Genome Are Associated with Elevated PSA Levels in Prostate Cancer Patients  Anita Kloss-Brandstätter, Georg Schäfer, Gertraud Erhart, Alexander Hüttenhofer, Stefan Coassin, Christof Seifarth, Monika Summerer, Jasmin Bektic, Helmut Klocker, Florian Kronenberg  The American Journal of Human Genetics  Volume 87, Issue 6, Pages (December 2010) DOI: /j.ajhg Copyright © 2010 The American Society of Human Genetics Terms and Conditions

2 Figure 1 HE Staining and Immunohistochemical Expression of p63 in Prostate Tissue Sections (A) 40-fold magnification of frozen sections showing HE staining of benign (A1 and A3, left side) and prostate cancer (A3, right side) tissue and immunohistochemical staining for the basal cell marker p63 (brown) with positive expression in benign (A2 and A4, left side) and negative expression in cancer glands (A4, right side). (B) 40-fold magnification of paraffin slides (from formalin-fixed tissue adjacent to the frozen material) showing HE staining of benign (B1) and prostate cancer (B3) tissue and immunohistochemical staining for p63 in benign cells (B2) and negative expression in cancer glands (B4). (C) 400-fold magnification of selected cut-outs of the slides shown in (B). (D) Example of a heteroplasmic mutation in MT-CO3 in the cancerous tissue of one sample, which was not present in the normal tissue. The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

3 Figure 2 Phylogenetic Tree Representing the Benign Profiles of 30 Prostate Cancer Patients and Four Lab Technicians The sequences are stored in GenBank (accession numbers HM625678–HM625711HM625678HM625679HM625680HM625681HM625682HM625683HM625684HM625685HM625686HM625687HM625688HM625689HM625690HM625691HM625692HM625693HM625694HM625695HM625696HM625697HM625698HM625699HM625700HM625701HM625702HM625703HM625704HM625705HM625706HM625707HM625708HM625709HM625710HM625711, corresponding to PCA001–PCA030 and Lab001–Lab004). The position of the rCRS is indicated for reading off sequence motifs. Mutations are transitions unless a base is explicitly indicated. The prefix designates reversions, whereas suffixes indicate transversions (to A, G, C, or T), indels (.1, d), and heteroplasmies (R, Y). The variation in number of Cs at nucleotide position 16193, 309, and 315 was not included in the phylogeny; detailed information regarding each mtDNA is available in Table S4. Point heteroplasmic mutations that were observed in benign tissue samples are highlighted in turquoise. The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

4 Figure 3 Distribution of All Observed Somatic Mutations over the Mitochondrial Genome Transfer RNAs are shaded in light blue. The location of the PCR fragments for the primary screen of entire mtDNA genomes (fragments A and B) and the secondary, targeted screen (fragments C and D) are indicated in the inner circle of the mtDNA. The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

5 Figure 4 Location of Somatic tRNA Mutations in the Secondary Structure of the tRNAs The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

6 Figure 5 Difference in PSA at Diagnosis between Patients with and without Somatic tRNA Mutations The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

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