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. 2024 Aug 26:39:101805.
doi: 10.1016/j.bbrep.2024.101805. eCollection 2024 Sep.

PIK3CA mutation analysis in circulating tumor cells of patients with hormone receptor positive metastatic breast cancer

Elena Marino  1   2 , Cristian Mauro  3 , Elena Belloni  4 , Marco Picozzi  3 , Valentina Favalli  5 , Maria Cristina Cassatella  3 , Laura Zorzino  3 , Luciano Giacò  6 , Pier Giuseppe Pelicci  4   7 , Massimo Barberis  1 , Maria Teresa Sandri  8 , Loris Bernard  1
Affiliations

PIK3CA mutation analysis in circulating tumor cells of patients with hormone receptor positive metastatic breast cancer

Elena Marino et al. Biochem Biophys Rep. .

Abstract

In metastatic breast cancer (MBC), blood is a source of circulating tumor cells (CTCs). CTCs may serve as a ''real-time liquid biopsy" as they represent metastatic tumor genetics better than primary tumor. PIK3CA is one of the most important oncogenes in treatment-unresponsive breast cancers. The aim of this study was to detect PIK3CA mutations and hereditary cancer variants in CTCs from MBC patients. Forty-seven blood samples were obtained from 20 MBC patients from at least 1/3 consecutive time points. CTCs were quantified using the CellSearch system and isolated from 11/20 patients with ≥5/7.5 ml CTCs (14/47 blood samples) using the DEPArray system. DNA was extracted and amplified to perform Sanger sequencing on PIK3CA gene. Sequencing revealed a pathogenic PIK3CA mutation in 2/11 (18 %) cases. Subsequently, we evaluated a 26-target hereditary gene panel by Next Generation Sequencing and identified a concomitant pathogenic mutation in the TP53 gene in a patient with a PIK3CA mutation. No pathogenic germline variants were found. Our data support the conclusion that CTCs analysis may be used to identify mutations in patients to identify those more likely to metastasize.

Keywords: (CTCs); (NGS); Circulating tumor cells; Liquid biopsy; Next generation sequencing.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
A – Study workflow; B– PIK3CA c.1636 C > A (p.Gln546Lys) in patient 17; C – PIK3CA c.1634A > G (p.Glu545Gly) in patient 18, D – Venn diagram of all variants. CTC u.c.: green border; CTC: light blue border; Metastasis: purple border; WBCs: red border. Red circle: 14 non-pathogenic variants common to all samples; light yellow: specific variants for each cell type; yellow: common variants in two different cell types; orange: common variants in three different cell types. E − Venn diagram of variants classified as class 3, 4, or 5 in CTC, Metastasis and CTC u.c. There is only one common variant for the three cells types. CTC u.c.: blue border; CTC: red border; Metastasis: green border. CTC, circulating tumor cell; NGS, next generation sequencing; QC, quality control; WBS, white blood cell; WGA, whole genome amplification. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
See this image and copyright information in PMC

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