Kumar Putcha, Balananda-Dhurjati Jia, Xu Rao Katkoori, Venkat Salih, Chura Shanmugam, Chandrakumar Jadhav, Trafina C. Bovell, Liselle P. Behring, Michael Callens, Tom Messiaen, Ludwine Bae, Sejong Grizzle, William E. P. Singh, Karan Manne, Upender Clinical Implications of Rabphillin-3A-Like Gene Alterations in Breast Cancer <div><p>For the rabphillin-3A-like (<i>RPH3AL</i>) gene, a putative tumor suppressor, the clinical significance of genetic alterations in breast cancers was evaluated. DNA and RNA were extracted from formalin-fixed, paraffin-embedded (FFPE) cancers and matching normal tissues. DNA samples were assessed for loss of heterozygosity (LOH) at the <i>17p13</i>.<i>3</i> locus of <i>RPH3AL</i> and the <i>17p13</i>.<i>1</i> locus of the tumor suppressor, <i>TP53</i>. <i>RPH3AL</i> was sequenced, and single nucleotide polymorphisms (SNPs) were genotyped. RNA samples were evaluated for expression of <i>RPH3AL</i>, and FFPE tissues were profiled for its phenotypic expression. Alterations in <i>RPH3AL</i> were correlated with clinicopathological features, LOH of <i>TP53</i>, and patient survival. Of 121 cancers, 80 had LOH at one of the <i>RPH3AL</i> locus. LOH of <i>RHP3AL</i> was associated with nodal metastasis, advanced stage, large tumor size, and poor survival. Although ~50% were positive for LOH at the <i>RPH3AL</i> and <i>TP53</i> loci, 19 of 105 exhibited LOH only at the <i>RPH3AL</i> locus. Of these, 12 were non-Hispanic Caucasians (Whites), 15 had large tumors, and 12 were older (>50 years). Patients exhibiting LOH at both loci had shorter survival than those without LOH at these loci (log-rank, P = 0.014). LOH at the <i>TP53</i> locus alone was not associated with survival. Analyses of <i>RPH3AL</i> identified missense point mutations in 19 of 125 cases, a SNP (C>A) in the 5’untranslated region at -25 (5’UTR-25) in 26 of 104, and a SNP (G>T) in the intronic region at 43 bp downstream to exon-6 (intron-6-43) in 79 of 118. Genotype C/A or A/A of the SNP at 5’UTR-25 and genotype T/T of a SNP at intron-6-43 were predominantly in Whites. Low levels of RNA and protein expression of <i>RPH3AL</i> were present in cancers relative to normal tissues. Thus, genetic alterations in <i>RPH3AL</i> are associated with aggressive behavior of breast cancers and with short survival of patients.</p></div> ffpe;breast cancers;survival;missense point mutations;TP 53. RPH 3AL;snp;rhp;RPH 3AL;tumor suppressor;rna;dna;17 p 13.1 locus;loh;TP 53 loci;RPH 3AL locus;utr;17 p 13.3 locus;TP 53 locus;RPH 3AL gene 2015-06-12
    https://plos.figshare.com/articles/dataset/_Clinical_Implications_of_Rabphillin_3A_Like_Gene_Alterations_in_Breast_Cancer_/1448174
10.1371/journal.pone.0129216