Breast Cancer Final Presentation

7/31/2019 Breast Cancer Final Presentation

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SUPERVISORDr. SURESH HEDAU

(Scientist-C)

ICPO ,NOIDA

P

RESNTED

B

Y

-ANJU KATHEL

M.Sc. BIOTECHNOLOGY


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INTRODUCTION

Breast cancer is the most commonly occurring femalecancer in the world .(Ferlay j BF,et.al.2001,)

Breast cancer accounts for 23% of all newly occurringcancers in women worldwide .

Represents 13.7% of all cancer deaths.(Globocan 2008, IARC 2010.)

In India, breast cancer is the second most commoncancer (after cervical cancer) with an estimated 115,251

new diagnoses.(Ferlay j SH, globocan 2008.)

The second most common cause of cancer-relateddeaths with 53,592 breast cancer deaths in 2008.


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BREASTCANCER

Cancer that forms intissues of thebreast, usually theducts (tubes that

carry milk to thenipple) and lobules(glands that makemilk). It occurs inboth men and

women, althoughmale breast canceris rare.

http://cancernet.nci.nih.gov/wyntk_pubs/breast.ht

m#2


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INCIDENCE OF BREAST CANCER

Indian Cancer Statistics; 28 march 2012


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Risk Factors that cause Breast Cancer

Factors that Cannot be

Prevented

Gender

Aging

Genetic Risk Factors(inherited)

Family History

Personal History

Race

Menstrual Cycle

Estrogen

Lifestyle Risks

Oral Contraceptive Use

Not Having Children

Hormone Replacement

Therapy Not Breast Feeding

Alcohol Use

Obesity

High Fat Diets

Physical Inactivity

Smoking


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BRCA 1 Gene

BRCA gene is a breast cancer susceptibty

gene,i.e. tumor suppressor gene responsible forboth normal development and carcinogenesis inbreast.

BRCA1, reveals multi functional protein involvedin DNA repair, Cell cycle regulation, transcriptionand apoptosis. (Mueller et.al. 2002)

BRCA1 mutations may play a significant role in the

tumor-genesis of familial breast cancer.

BRCA1Protein play vital roles in genomic stabilityand can act as tumor suppressors in both men and

women. (Powell, S., Kachni, L., 2003).


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Gene locationThe human BRCA1 geneis located on the long (q)arm of chromosome 17 at

region 2 band 1, frombase pair 38,429,551 tobase pair 38,551,283.

(X Yang et.al2001.)


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Structure of BRCA 1

Cloned in 1994 (Miki et al) Mapped to chromosome 17q21

5,592kb long

24 exons


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BRCA-1 Consists of 1863 amino acids

Expressed in most proliferation cells

Part of large protein complex

3 MDa

BRCT (C-terminal of BRCA) domain

Consists of 2 conserved BRCT repeats~90-100amino acids long

N-terminal ring-finger domain(Irene Guendel.et.al.2010)


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It is the covalent addition of methyl groupto 5th Position of cystosine with in CpG di-

nucleotides which are frequently located in

the promoter region of genes. (Novik et.al.2002)

It is a complex process catalyzed by DNA

methyl transferase. The addition of themethyl group from the universal methyl

Donor s-adenosyl Lmethionine.(X Yang et.al.2001)


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FIG:METHYLATION OF CpG


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Aberrant methylation of BRCA1 CpG island

Promoter is associated with decreased BRCA1mRNA in sporadic breast cancer cells.

There is a strong relationship between BRCA1promoter hyper-methylation and the existence ofLOH (loss of hetero-zygosity) at the BRCA locus.

This finding suggested that one allele has beenlost by deletion and the other is inactivated byaberrant methylation. Both events simultaneouslyleading to the bi-allelic inactivation and complete

lack of function of the BRCA1 gene.


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The frequent loss of BRCA1 protein

In sporadic breast carcinoma could also result

from epigenetic inactivation of both parental alleles.

Reduced BRCA1 protein expression in tumors ofpatients with poor survival prognosis provides the

evidence of this protein as a prognostic factor inpatients with sporadic breast carcinoma.


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OBJECTIVES1. TO INVESTIGATE THE BRCA1 PROMOTER

METHYLATION IN SPORADIC BREASTCANCERS.

2. TO INVESTIGATE THE EXPRESSION OF BRCA1IN SPORADIC BREAT CANCERS.

3. TO CORRELATE THE PROMOTER

METHYLATION STATUS AND GENEEXPRESSION LEVEL WITH DIFFERENT CLINIC-PATHOLOGICAL STAGES OF THE BEASTCANCER.


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MATERIALS AND METHOD

Clinical specimens: 20 Tissue biopsies.

DNA ISOLATION PROTEIN ISOLATION

& ESTIMATION & ESTIMATION

DNA BISULPHITE MODIFICATION SDS- PAGE

qMS - PCR

DNA ESTIMATION BY WESTERN BLOTTING

2.5% AGAROSE GEL AGAROSE


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References1. Ferlay J BF, Pisani P, Parkin DM. GLOBOCAN 2000: Cancer Incidence,

Mortality and Prevalence Worldwide, Version 1.0. 2001.

2. Ferlay J SH, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008

v1.2, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10

[Internet]. 2010 [cited 2011 October 25, 2011]; Available from:

3.Indian cancer statistics, 28 march 2012.

4. Christopher R Mueller1 and Calvin D Roskelley1 2002

1Cancer Research Laboratories, Queens University, Kingston, Ontario,

Canada.

5. X Yang, L Yan and NE Davidson ,Breast cancer program,2001


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Documents

Breast Cancer Final Presentation