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. 2020 May;28(5):607-614.
doi: 10.1016/j.jsps.2020.03.013. Epub 2020 Apr 2.

Association of mutation and low expression of the CTCF gene with breast cancer progression

Md Salman Akhtar  1   2 , Naseem Akhter  1   2 , Mohammad Zeeshan Najm  3 , S V S Deo  4 , N K Shukla  4 , Shaia Saleh R Almalki  2 , Raed A Alharbi  2 , Abdulmajeed Abdulghani A Sindi  2 , Abdulmohsen Alruwetei  5 , Abrar Ahmad  6 , Syed Akhtar Husain  1
Affiliations

Association of mutation and low expression of the CTCF gene with breast cancer progression

Md Salman Akhtar et al. Saudi Pharm J. 2020 May.

Abstract

Background: CTCF encodes 11-zinc finger protein which is implicated in multiple tumors including the carcinoma of the breast. The Present study investigates the association of CTCF mutations and their expression in breast cancer cases.

Methods: A total of 155 breast cancer and an equal number of adjacent normal tissue samples from 155 breast cancer patients were examined for CTCF mutation(s) by PCR-SSCP and automated DNA sequencing. Immunohistochemistry (IHC) method was used to analyze CTCF expression. Molecular findings were statistically analyzed with various clinicopathological features to identify associations of clinical relevance.

Results: Of the total, 16.1% (25/155) cases exhibited mutation in the CTCF gene. Missense mutations Gln > His (G > T) in exon 1 and silent mutations Ser > Ser (C > T) in exon 4 of CTCF gene were analyzed. A significant association was observed between CTCF mutations and some clinicopathological parameters namely menopausal status (p = 0.02) tumor stage (p = 0.03) nodal status (p = 0.03) and ER expression (p = 0.04). Protein expression analysis showed 42.58% samples having low or no expression (+), 38.0% with moderate (++) expression and 19.35% having high (+++) expression for CTCF. A significant association was found between CTCF protein expression and clinicopathological parameters include histological grade (p = 0.04), tumor stage (p = 0.04), nodal status (p = 0.03) and ER status (p = 0.04).

Conclusions: The data suggest that CTCF mutations leading to its inactivation significantly contribute to the progression of breast cancer.

Keywords: Breast cancer; CTCF; Immunohistochemistry; Mutation; PCR-SSCP.

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Figures

Fig. 1
Fig. 1
Amplified exon products (206 and 246 bp) of CTCF gene. Lane L: Molecular marker of 100 bp, Lanes 1–7: Amplicons from the Breast cancer tissues samples.
Fig. 2
Fig. 2
SSCP (non-radio active) analysis of CTCF gene shows a variation/ shift in band pattern lane 2, 3, 5, 6, 7 and 8 of the breast tumor samples when compared with normal sample in lane 1.
Fig. 3
Fig. 3
Representative partial electropherograms of Mutant (B) (shown by arrow) with Normal (A) adjacent forms of CTCF gene showing substitutin G>T.
Fig. 4
Fig. 4
Impact of mutation on CTCF protein.
Fig. 5
Fig. 5
Representative Immunohistochemical slides (seen at 10X) showing (a) Low expression (+), (b) Moderate expression (++), (c) High expression (+++) of CTCF protein in Indian female breast cancer cases and (d) CTCF protein expression in normal control.
Fig. 6
Fig. 6
Graphical abstract.
See this image and copyright information in PMC

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