Disease relevance of PPP2R1B

• Alterations of the PPP2R1B gene in human lung and colon cancer [1].
• Absence of PPP2R1B gene alterations in primary ovarian cancers [2].
• Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers [3].
• The codon 90 Gly > Asp alteration may represent a non-pathological polymorphism and consequently the mutation frequency reported in lung cancers may have been overstated and the designation of PPP2R1B as a tumor suppressor gene should be regarded with caution [2].
• 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 [4].

High impact information on PPP2R1B

• Several independent studies indicate that multiple tumor-suppressor genes are found in this region, including the gene PPP2R1B at 11q23-24 (ref. 7). Linkage studies of NSCLC are precluded because no hereditary forms are known [5].
• Sequencing of the PPP2R1B gene, located on human chromosome 11q22-24, revealed somatic alterations in 15% (5 out of 33) of primary lung tumors, 6% (4 out of 70) of lung tumor-derived cell lines, and 15% (2 out of 13) of primary colon tumors [1].
• These findings suggested that both PPP2R1A and PPP2R1B may be tumor suppressor genes [6].
• Varying proportions of alterations were detected, ranging from 6% in PPP2R1B to 39% in PIG8 [7].
• Most of the mutations affecting PPP2R1B were exons deletions, suggesting abnormal splicing [4].

Chemical compound and disease context of PPP2R1B

• BACKGROUND/AIMS: In 1998 the PPP2R1B gene encoding the A subunit of the serine/threonine protein phosphatase was identified as a putative tumour suppressor gene in lung and colon cancer in the chromosome region 11q22-24 [3].

Biological context of PPP2R1B

• PPP2R1B is located on chromosome 11q22-24 which coincides with the site of frequent loss of heterozygosity (LOH) in ovarian cancer [2].
• LOH at the PPP2R1B locus was detected in 32% of the malignant tumors but no somatic alterations were detected in any of 65 malignant, five borderline or six benign tumors [2].
• We investigated if the PPP2R1B gene was inactivated in ovarian cancer by single strand conformational polymorphism (SSCP) and heteroduplex (HD) analysis of 99% of the coding region [2].
• Alterations in the suppressor gene PPP2R1B in parathyroid hyperplasias and adenomas [8].
• Missense mutations and homozygous deletions of the PPP2R1B gene were found in 4 of 50 patients (8%) and in 1 of 50 patients, respectively, with colorectal cancers [9].

Associations of PPP2R1B with chemical compounds

• The PPP2R1B gene, which encodes the beta isoform of the A subunit of the serine/threonine protein phosphatase 2A (PP2A), was identified as a putative human tumor suppressor gene [1].
• Mutations of the PPP2R1B gene, which encodes the Abeta scaffolding subunit of serine/threonine protein phosphatase 2A (PP2A), have been identified in several types of cancer including lung and breast carcinoma [10].

Other interactions of PPP2R1B

• One region is bracketed by markers D11S1647 and NCAM2 and contains the gene encoding the beta isoform of the A subunit of the human protein phosphatase 2A (PPP2R1B) [11].
• Because the protein phosphatase 2 regulatory subunit A beta isoform gene (PPP2R1B) maps within the critical region of hereditary paraganglioma (PGL1) on chromosomal band 11q23, we characterized its genomic structure and evaluated it as a candidate gene for PGL1 [12].
• We performed polymerase chain reaction-based single-strand conformation polymorphism and direct sequencing on six parathyroid hyperplasias and 12 adenomas to evaluate the role of PPP2R1B in the pathogenesis of parathyroid lesions [8].

Analytical, diagnostic and therapeutic context of PPP2R1B

• Finally, characterization of candidate tumor suppressor gene PPP2R1B, which encodes for a subunit of protein phosphatase 2A (PP2A), showed seemingly insignificant alterations by cDNA sequence analysis [13].
• To evaluate the role of the PPP2R1B gene in the pathogenesis of CLL and MCL, we performed RT-PCR analysis and cDNA sequencing on 10 CLL RNA samples and SSCP analysis on 26 CLL and 37 MCL genomic DNA samples [14].
• Deletions and/or point mutations within 412-601 amino acid sequences (binding regions of PP2A-C protein) of the PPP2R1B gene derived from colorectal cancer tissues inhibited co-immunoprecipitation of PP2A-Abeta and PP2A-C proteins [9].

References