Secondary Logo

Journal Logo

SINGLE NUCLEOTIDE POLYMORPHISMS (SNPs) OF EXONS 3, 4, 5 AND 9 OF THE MATRIX METALLOPROTEINASE 2 (MMP‐2) GENE IN BREAST CARCINOMA OF MALAYSIAN WOMEN USING HIGH RESOLUTION MELTING ANALYSIS

Rahman, Sabariah Abdul1,2; Choy, Chan Soon1,2; Rosli, Rozita1,2; Hussain, Sharifah Noor Akmal Syed3; Abdullah, Noor Hisham4

Pathology - Journal of the RCPA: 2009 - Volume 41 - Issue - p 74–75
General Poster Display
Free

1Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Selangor;

2UPM‐MAKNA Cancer Research Laboratory, Institute Of Biosciences, Universiti Putra Malaysia (UPM), Selangor;

3Department of Pathology, Faculty of Medicine, Hospital Universiti Kebangsaan Malaysia (HUKM), Kuala Lumpur;

4Department of Surgery, Putrajaya Hospital, Putrajaya, Malaysia

Background: Breast cancer metastasis is a factor contributing to high disease mortality. Single nucleotide polymorphism (SNP) of the matrix metalloproteinase 2 (MMP‐2) gene, which controls the enzyme for degradation of macromolecules of the connective tissues and extracellular matrix, has been associated with cancer invasion and metastasis.

Aim: The aim was to detect SNPs of exons 3, 4, 5 and 9 of the MMP‐2 gene in breast carcinoma of Malaysian women using high resolution melting analysis (HRM).

Methods: Genomic DNA was obtained of both tumour mass and normal adjacent tissue from 60 Malaysian breast cancer patients. SNP scanning involving all four exons of MMP‐2 coding regions was performed by HRM analysis on Rotor‐Gene 6000 real‐time PCR. The PCR products presented with aberrant melting curve pattern were purified and sequenced. Sequence trace data obtained were analysed with Staden Package for mutation detection.

Results: The scanning of the MMP‐2 exons detected 4 known SNPs in exon 5 (678G>C, 750C>T), intron 5 (832+12C>T) and exon 9 (1380G>A). No SNP was detected on exon 3 and 4. Five patients carried both copies of variant A SNP 1380G>A while only one patient carried homozygous variant T SNP 832+12C>T. Only one patient with homozygous variant T allele SNP 1380G>A and SNP 678G>C had poor outcome with extensive metastasis and failed chemotherapy.

Conclusion: A relationship between SNP of MMP‐2 with disease progression and poor therapeutic response is a strong possibility. The utilisation of HRM, a sensitive and cost effective method for scanning the MMP‐2 gene, is suggested on all exons to elucidate the involvement of SNPs in cancer progression.

© 2009 Royal College of Pathologists of Australasia