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Plasma-SeqSensei™ BC RUO Kit

Plasma-SeqSensei (PSS) BC RUO Kit allows for the highly sensitive and specific detection of mutations in circulating tumour DNA (ctDNA) from the plasma of patients with breast cancer.

The kit is based on the next-generation sequencing technology and covers key gene mutations such as AKT1, ERBB2, ESR1, KRAS, PIK3CA and TP53 to detect established and emerging predictive markers, resistance mutations, and frequently occurring genetic alterations in breast cancer. These genes significantly contribute to the development of breast cancer and are important biomarkers utilised for the choice of therapy, prognosis as well as monitoring of recurrence and therapy response. [1]

The different breast cancer subtypes show different mutational patterns, which affect response to treatment and prognosis. [2] For example, luminal A tumours present a higher proportion of PIK3CA mutations (49%), whereas basal-like tumours have mostly TP53 mutations (84%).

Identifying patients with PIK3CA mutations who may benefit from PI3K-targeted therapy could help in guiding treatment decisions. The PIK3CA mutations have also shown prognostic value as they are associated with an improved invasive disease-free survival. [3]

A comprehensive profiling of AKT1-E17K may help define a potential role for the mutation in the development and progression of breast cancer. [4]

ESR1 mutations are a marker of resistance to endocrine therapy, usually arising in patients treated with aromatase inhibitors in the adjuvant and metastatic settings. [5] Their detection could be used to monitor disease progression.

For the configuration of the Plasma-SeqSensei BC RUO kits, six key cancer genes were selected after comparison of mutation frequencies using the COSMIC (Catalogue of Somatic Mutation in Cancer) and cBioPortal for cancer genomics databases.

Features

Mutation frequencies are listed in the table below:

Breast cancer

  COSMIC (7) cBioPortal (8)
AKT1 4% 3%
ERBB2 6%* 3%
ESR1 12%* 4%
KRAS 2% 1%
PIK3CA 31% 36%
TP53 36% 34%

 

Most frequent mutations detected by Plasma-SeqSensei BC RUO panel:

Gene Most frequent mutations in BC
AKT1 E17K
ERBB2 S310F, L755S
ESR1 D538G, Y537S
KRAS G12D, G12V, G13D, G12C, G12R, G12A, G12S
PIK3CA E545K, H1047R, E542K, H1047L, N345K, E545A, C420R
TP53 R175H, R248Q, R273H, R282W, R213*, G245S, Y220C, R273C

Plasma-SeqSensei BC RUO Kit is for Research Use Only. Not for use in diagnostic procedures.

 

References

  1. Sotiriou & Brandão. Multigene sequencing in breast cancer: ESMO biomarker factsheet. https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/multigene-sequencing-in-breast-cancer, 2019.
  2. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490, 61-70, 2012.
  3. Zardavas et al. Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data. JCO 36 (10), 981-990, 2018.
  4. Rudolph et al. AKT1 E17K mutation profiling in breast cancer: prevalence, concurrent oncogenic alterations, and blood-based detection. BMC Cancer 16, 622, 2016.
  5. Spoerke et al. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun 7, 11579, 2016.
  6. https://cancer.sanger.ac.uk/cosmic
  7. https://www.cbioportal.org/
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