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Fig. 2 | Molecular Cancer

Fig. 2

From: Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases

Fig. 2

FHIT is preferentially methylated compared to known epigenetically regulated tumor suppressors (SHP1, CDKN1A, and CDKN2A) in ATL patients’ samples. a Representation of global MSPCR methylation patterns in a healthy, non-HTLV-I infected, PBMC, an HTLV-I (+) cell line, and identical acute ATL (n = 10) patients’ samples for FHIT, SHP1, CDKN1A, and CDKN2A. MSPCR bands amplifying the unmethylated (U) or methylated (M) product are represented. b The FHIT gene is methylated in acute ATL patients’ samples (n = 25) compared to SHP1, CDKN1A, and CDKN2A. The overall percentage of unmethylated (blue) or methylated (red) FHIT, SHP1, CDKN1A, and CDKN2A MSPCR products in identical acute ATL patients’ samples is graphed. c BSG analysis of individual CpG islands in the FHIT, SHP1, CDKN1A, and CDKN2A genes of corresponding ATL patients. BSG was used to determine the methylation pattern of MT4 (an HTLV-I+ cell line), a HD, and six identical acute ATL patients’ samples (A-1 through A-6). Unmethylated and methylated alleles are noted by white and black boxes, respectively; and each horizontal line represents a single amplified clone. d The FHIT gene does not show variations in methylation in different clinical subtypes of ATL. BSG sequencing was used to identify the global BSG methylation pattern of FHIT and miR-124a in eight identical acute ATL patients’ samples (A-7 through A-14), and eight identical smoldering ATL patients’ samples (S23-S30). e Graphical representation of the overall percentage of methylated (M) CpG islands (n = 31) in the FHIT gene and miR-124 microRNA (n = 16) in acute (ATL-A), chronic (ATL-C), and smoldering (ATL-S) samples from eight identical ATL patients. Patients are graphed from zero CpG islands methylated (0%) to complete CpG islands methylated (100%) in the analyzed portion of the FHIT and miR-124a genes. The values plotted represent an average value from sequencing of several BGSs. p-values were calculated by one-way ANOVA statistical test between the three groups

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