PIK3CA mutations in breast cancer: A Tunisian series.

BackgroundThe aim of this study was to analyze PIK3CA mutations in exons 9 and 20 in breast cancers (BCs) and their association with clinicopathological characteristics.MethodsMutational analysis of PIK3CA exon 9 and 20 was performed by Sanger sequencing in 54 primary BCs of Tunisian women. The associations of PIK3CA mutations with clinicopathological characteristics were analyzed.ResultsFifteen exon 9 and exon 20 PIK3CA variants were identified in 33/54 cases (61%). PIK3CA mutations including pathogenic (class 5/Tier I) or likely pathogenic (class 4/Tier II) occurred in 24/54 cases (44%): 17/24 cases (71%) in exon 9, 5/24 cases (21%) in exon 20 and 2/24 cases (8%) in both exons. Of these 24 cases, 18 (75%) carried at least one of the three hot spot mutations: E545K (in 8 cases), H1047R (in 4 cases), E542K (in 3 cases), E545K/E542K (in one case), E545K/H1047R (in one case) and P539R/H1047R (in one case). Pathogenic PIK3CA mutations were associated with negative lymph node status (p = 0.027). Age distribution, histological SBR tumor grading, estrogen and progesterone receptors, human epidermal growth factor receptor 2, and molecular classification were not correlated with PIK3CA mutations (p > 0.05).ConclusionThe frequency of somatic PIK3CA mutations in BCs of Tunisian women is slightly higher than that of BCs of Caucasian women and more observed in exon 9 than in exon 20. PIK3CA mutated status is associated with negative lymph node status. These data need to be confirmed in larger series

Primer sequences, annealing temperatures and product lengths.

Primer sequences, annealing temperatures and product lengths.</p

<i>PIK3CA</i> variant’s classification according to the American College of Medical Genetics and Genomics guidelines.

PIK3CA variant’s classification according to the American College of Medical Genetics and Genomics guidelines.</p

Summary of variants annotation using the reference sequence NM_006218.4 and classification according to ACMG.

Summary of variants annotation using the reference sequence NM_006218.4 and classification according to ACMG.</p

Association between PIK3CA mutations and clinicopathological characteristics of breast cancer.

Association between PIK3CA mutations and clinicopathological characteristics of breast cancer.</p

Fig 1 -

Electropherograms of the 15 PIK3CA variants identified in breast cancers (A) Known PIK3CA mutations (B) Novel variants. All sequences are in sense strand. Red rectangle box shows the position of the mutations. The major peak corresponds to the normal nucleotide and the minor peak corresponds to the mutant nucleotide. Altered nucleotide and amino acid positions and related codon substitution are shown of each corresponding sequence.</p

Prediction function and conservation of variants with unknown functions.

Prediction function and conservation of variants with unknown functions.</p

Distribution of mutation spectrum among breast cancer cases.

(A) Frequencies of the fifteen identified PIK3CA variants among breast cancer samples. (B) Proportion of samples with class 5 and 4 mutations. (C) Proportion of samples with concomitant or single mutations. (D) Proportion of samples with pathogenic class 5 and 4 PIK3CA mutations.</p