High Mutability of the Tumor Suppressor Genes RASSF1 and RBSP3 (CTDSPL) in Cancer

BACKGROUND:Many different genetic alterations are observed in cancer cells. Individual cancer genes display point mutations such as base changes, insertions and deletions that initiate and promote cancer growth and spread. Somatic hypermutation is a powerful mechanism for generation of different mutations. It was shown previously that somatic hypermutability of proto-oncogenes can induce development of lymphomas. METHODOLOGY/PRINCIPAL FINDINGS:We found an exceptionally high incidence of single-base mutations in the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) both located in 3p21.3 regions, LUCA and AP20 respectively. These regions contain clusters of tumor suppressor genes involved in multiple cancer types such as lung, kidney, breast, cervical, head and neck, nasopharyngeal, prostate and other carcinomas. Altogether in 144 sequenced RASSF1A clones (exons 1-2), 129 mutations were detected (mutation frequency, MF = 0.23 per 100 bp) and in 98 clones of exons 3-5 we found 146 mutations (MF = 0.29). In 85 sequenced RBSP3 clones, 89 mutations were found (MF = 0.10). The mutations were not cytidine-specific, as would be expected from alterations generated by AID/APOBEC family enzymes, and appeared de novo during cell proliferation. They diminished the ability of corresponding transgenes to suppress cell and tumor growth implying a loss of function. These high levels of somatic mutations were found both in cancer biopsies and cancer cell lines. CONCLUSIONS/SIGNIFICANCE:This is the first report of high frequencies of somatic mutations in RASSF1 and RBSP3 in different cancers suggesting it may underlay the mutator phenotype of cancer. Somatic hypermutations in tumor suppressor genes involved in major human malignancies offer a novel insight in cancer development, progression and spread

Measurement of the e+e−→π+π−e^+e^-\to\pi^+\pi^- cross section from threshold to 1.2 GeV with the CMD-3 detector

The cross section of the process $e^+e^-\to\pi^+\pi^-$ has been measured in the center of mass energy range from 0.32 to 1.2 GeV with the CMD-3 detector at the electron-positron collider VEPP-2000. The measurement is based on a full dataset collected below 1 GeV during three data taking seasons, corresponding to an integrated luminosity of about 62 pb$^{-1}$. In the dominant $\rho$-resonance region, a systematic uncertainty of 0.7% has been reached. At energies around $\phi$-resonance the $\pi^+\pi^-$ production cross section was measured for the first time with high energy resolution. The forward-backward charge asymmetry in the $\pi^+\pi^-$ production has also been measured. It shows the strong deviation from the theoretical prediction based on conventional sQED framework and is in good agreement with GVDM and dispersive-based predictions. The impact of presented results on the evaluation of the hadronic contribution to the anomalous magnetic moment of muon is discussed.Comment: 52 pages, 36 figures; cosmetic changes of the text, fix fig.2 , fix comment on used selection cuts in the attached radiative correction tabl

Measurement of the pion formfactor with CMD-3 detector and its implication to the hadronic contribution to muon (g-2)

The cross section of the process $e^+e^-\to\pi^+\pi^-$ has been measured in the center of mass energy range from 0.32 to 1.2 GeV with the CMD-3 detector at the electron-positron collider VEPP-2000. The measurement is based on an integrated luminosity of about 88 pb$^{-1}$ out of which 62 pb$^{-1}$ constitutes a full dataset collected by CMD-3 at center-of-mass energies below 1 GeV. In the dominant region near $\rho$-resonance a systematic uncertainty of 0.7% has been reached. The impact of presented results on the evaluation of the hadronic contribution to the anomalous magnetic moment of muon is discussed.Comment: 6 pages, 3 figure