G2Cdb::Human Disease report

Disease id
D00000008
Name
Melanoma
Nervous system disease
no

Genes (2)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001444 PPP2R1A
protein phosphatase 2, regulatory subunit A, alpha
Y (10713707) Single nucleotide polymorphism (SNP) ?
G00001444 PPP2R1A
protein phosphatase 2, regulatory subunit A, alpha
Y (10713707) Single nucleotide insertion (SNI) ?
G00002235 CTNNB1
catenin (cadherin-associated protein), beta 1, 88kDa
Y (9065403) Microinsertion (MI) Y
G00002235 CTNNB1
catenin (cadherin-associated protein), beta 1, 88kDa
Y (11930117) Deletion (D) N

References

  • Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines.

    Pollock PM and Hayward N

    Joint Experimental Oncology Program of the Queensland Institute of Medical Research, The University of Queensland, and the Queensland Cancer Fund, P.O. Royal Brisbane Hospital, Herston 4029, Australia.

    Mutations in exon 3 of the CTNNB1 gene encoding beta-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting beta-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-1/wingless pathway through activation of beta-catenin is a rare event, even in melanoma cell lines.

    Melanoma research 2002;12;2;183-6

  • Low frequency of alterations of the alpha (PPP2R1A) and beta (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms.

    Calin GA, di Iasio MG, Caprini E, Vorechovsky I, Natali PG, Sozzi G, Croce CM, Barbanti-Brodano G, Russo G and Negrini M

    Dipartimento di Medicina Sperimentale e Diagnostica, Sezione di Microbiologia, Universitá di Ferrara, via Luigi Borsari, 46, I-44100 Ferrara, Italy.

    The phosphatase 2A (PP2A) is one of the major cellular serine-threonine phosphatases. It was recently shown that the gene encoding for the beta isoform of its subunit A, PPP2R1B, is altered in human lung and colorectal carcinomas, suggesting a role in human tumorigenesis. Here, we report the detection of mutations in breast, lung carcinomas and melanomas in the genes of both alpha (PPP2R1A) and beta isoforms. Mutations affecting PPP2R1B were found in four breast carcinomas, while mutations in PPP2R1A were found in carcinomas of the breast and of the lung and in one melanoma. Most of the mutations affecting PPP2R1B were exons deletions, suggesting abnormal splicing. These splicing abnormalities were detected in tumor samples in the absence of the normal splicing product, and were not found in several normal controls. In one case, a homozygous deletion present in tumor DNA, and not in the matched normal control was demonstrated. Mutations affecting the PPP2R1A gene were nucleotide substitutions changing highly conserved amino acids and one frame-shift. Although the frequency of alterations is low, the inclusion of both isoforms of subunit A in the genes mutated in human cancer and the addition of breast cancer to the list of neoplasms in which PPP2R1B is altered, strengthen the potential role of PP2A in human tumorogenesis.

    Oncogene 2000;19;9;1191-5

  • Stabilization of beta-catenin by genetic defects in melanoma cell lines.

    Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E and Polakis P

    Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.

    Signal transduction by beta-catenin involves its posttranslational stabilization and downstream coupling to the Lef and Tcf transcription factors. Abnormally high amounts of beta-catenin were detected in 7 of 26 human melanoma cell lines. Unusual messenger RNA splicing and missense mutations in the beta-catenin gene (CTNNB1) that result in stabilization of the protein were identified in six of the lines, and the adenomatous polyposis coli tumor suppressor protein (APC) was altered or missing in two others. In the APC-deficient cells, ectopic expression of wild-type APC eliminated the excess beta-catenin. Cells with stabilized beta-catenin contained a constitutive beta-catenin-Lef-1 complex. Thus, genetic defects that result in up-regulation of beta-catenin may play a role in melanoma progression.

    Funded by: NCI NIH HHS: 1R43CA69931

    Science (New York, N.Y.) 1997;275;5307;1790-2

Literature (3)

Pubmed - human_disease

  • Low frequency of alterations of the alpha (PPP2R1A) and beta (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms.

    Calin GA, di Iasio MG, Caprini E, Vorechovsky I, Natali PG, Sozzi G, Croce CM, Barbanti-Brodano G, Russo G and Negrini M

    Dipartimento di Medicina Sperimentale e Diagnostica, Sezione di Microbiologia, Universitá di Ferrara, via Luigi Borsari, 46, I-44100 Ferrara, Italy.

    The phosphatase 2A (PP2A) is one of the major cellular serine-threonine phosphatases. It was recently shown that the gene encoding for the beta isoform of its subunit A, PPP2R1B, is altered in human lung and colorectal carcinomas, suggesting a role in human tumorigenesis. Here, we report the detection of mutations in breast, lung carcinomas and melanomas in the genes of both alpha (PPP2R1A) and beta isoforms. Mutations affecting PPP2R1B were found in four breast carcinomas, while mutations in PPP2R1A were found in carcinomas of the breast and of the lung and in one melanoma. Most of the mutations affecting PPP2R1B were exons deletions, suggesting abnormal splicing. These splicing abnormalities were detected in tumor samples in the absence of the normal splicing product, and were not found in several normal controls. In one case, a homozygous deletion present in tumor DNA, and not in the matched normal control was demonstrated. Mutations affecting the PPP2R1A gene were nucleotide substitutions changing highly conserved amino acids and one frame-shift. Although the frequency of alterations is low, the inclusion of both isoforms of subunit A in the genes mutated in human cancer and the addition of breast cancer to the list of neoplasms in which PPP2R1B is altered, strengthen the potential role of PP2A in human tumorogenesis.

    Oncogene 2000;19;9;1191-5

  • Stabilization of beta-catenin by genetic defects in melanoma cell lines.

    Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E and Polakis P

    Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.

    Signal transduction by beta-catenin involves its posttranslational stabilization and downstream coupling to the Lef and Tcf transcription factors. Abnormally high amounts of beta-catenin were detected in 7 of 26 human melanoma cell lines. Unusual messenger RNA splicing and missense mutations in the beta-catenin gene (CTNNB1) that result in stabilization of the protein were identified in six of the lines, and the adenomatous polyposis coli tumor suppressor protein (APC) was altered or missing in two others. In the APC-deficient cells, ectopic expression of wild-type APC eliminated the excess beta-catenin. Cells with stabilized beta-catenin contained a constitutive beta-catenin-Lef-1 complex. Thus, genetic defects that result in up-regulation of beta-catenin may play a role in melanoma progression.

    Funded by: NCI NIH HHS: 1R43CA69931

    Science (New York, N.Y.) 1997;275;5307;1790-2

Pubmed - other

  • Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines.

    Pollock PM and Hayward N

    Joint Experimental Oncology Program of the Queensland Institute of Medical Research, The University of Queensland, and the Queensland Cancer Fund, P.O. Royal Brisbane Hospital, Herston 4029, Australia.

    Mutations in exon 3 of the CTNNB1 gene encoding beta-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting beta-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-1/wingless pathway through activation of beta-catenin is a rare event, even in melanoma cell lines.

    Melanoma research 2002;12;2;183-6

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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