Clinical Implications of Rabphillin-3A-Like Gene Alterations in Breast Cancer
Balananda-Dhurjati Kumar Putcha
Xu Jia
Venkat Rao Katkoori
Chura Salih
Chandrakumar Shanmugam
Trafina Jadhav
Liselle C. Bovell
Michael P. Behring
Tom Callens
Ludwine Messiaen
Sejong Bae
William E. Grizzle
Karan P. Singh
Upender Manne
10.1371/journal.pone.0129216
https://plos.figshare.com/articles/dataset/_Clinical_Implications_of_Rabphillin_3A_Like_Gene_Alterations_in_Breast_Cancer_/1448174
<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>
2015-06-12 03:59:24
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