Oncotarget: Determination of HER oncogene co-amplifications in breast cancer

Oncotarget recently published "Working together for the family: determination of HER oncogene co-amplifications in breast cancer" which reported that despite specific treatment, unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance.

In addition, the authors developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs.

On 111 IDC, the HER2 MLPA results were validated by FISH, CISH, and IHC.

The percentage of cells with HER2 co-amplified varied among the tumors.

Independent in-silico findings show that the outcome of HER2 patients is conditioned by the status of HER3 and HER4. The Oncotarget author's results encourage further studies to investigate the relationship with the patient's response to single or combined treatment.

The Oncotarget author's results encourage further studies to investigate the relationship with the patient's response to single or combined treatment.

Dr. Maria Roqué said, "The human epidermal growth factor receptor HER2 (ErbB2, HGNC: 3430) is a well-studied tyrosine kinase (TK) membrane receptor which functions as a therapeutic target in invasive ductal breast carcinomas (IDC)."

Gene family is a set of genes with a common ancestral origin, which participate typically in similar biological functions encoding for functionally related proteins.

Some well-known examples are the homeobox gene family, myosin gene family, and heat shock protein family.

HER2 also belongs to a gene family, with four members.

Figure 9: Co-amplification of HER2 with other family members determined by MLPA-ddPCR. Each panel shows the fluorescence amplitude of HEX (HER2) on the X axis vs FAM (other HER) on the Y axis. Dots represent fluorescence of Taqman probes hybridized to MLPA probe, in one cell contained in a droplet. Diploid cells and empty droplets are represented as grey dots. Cells with increased HER1, HER3 or HER4 copies are represented in blue dots and cells with amplified HER2 are represented in green. Cells with co-amplified genes (containing both, HER2 plus HER1, HER3 or HER4 amplifications) are shown as orange dots (see more details in Table 3). As can be seen, in the HER2+ tumor panels, higher co-amplification percentages are observed especially in FITR39. In the HER2- tumor panel, FITR8 (HER3 and HER4 positive, determined by standard MLPA) presents very low co-amplification percentages of HER2 with other HERs since HER2 is not considered amplified by standard MLPA. In FITR21 no amplification is observed.

In this work, they aimed to develop an original experimental approach to study simultaneously the gene amplification of all the HER family members in breast tumors and to determine the percentage of a tumor in which co-amplifications occur in the same cell.

The Roqué Research Team concluded in their Oncotarget Research Paper that they have also demonstrated the feasibility of quantifying the co-amplified tumor proportion by MLPA-ddPCR.

Their development encourages and facilitates further studies to investigate prospectively the association of co-amplified HERs with patient's outcome parameters such as overall survival and relapse-free survival.

It also permits the investigation of any relationship between the co-amplified tumor proportion and the patient response to single or combined treatment.

Such studies would help to determine whether the assessment of the HER family is a reliable predictive marker for anti-HER2 treatment response and/or combined anti-HER therapies selection.

Finally, the observations arising from breast cancer studies could serve as proof of principle for other tumors that commonly present the alteration of HER members.

DOI - https://doi.org/10.18632/oncotarget.27671

Full text - https://www.oncotarget.com/article/27671/text/

Correspondence to - Maria Roqué - mroque@mendoza-conicet.gob.ar

Keywords - HER oncogenes, breast cancer, MLPA, digital PCR, co-amplification

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