Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Cancer Research and Clinical Oncology
Published in: Journal of Cancer Research and Clinical Oncology 11/2007

01-11-2007 | Original Paper

Novel germline mutations in BRCA2 gene among 96 hereditary breast and breast–ovarian cancer families from Kerala, South India

Authors: Vani Syamala, Leelakumari Sreeja, Volga S. Syamala, B. Vinodkumar, Praveenkumar B. Raveendran, Hariharan Sreedharan, Ratheesan Kuttappan, Lekshmi Balakrishnan, Ravindran Ankathil

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2007

Login to get access

Abstract

Purpose

Aim of the present study was to identify the genetic heterogeneity, prevalence and frequency of germline mutations of BRCA2 gene in Hereditary Breast/Ovarian cancer patients from Kerala, South India.

Methods

We analyzed 102 Breast/Ovarian cancer patients from 96 breast and/ovarian cancer families for BRCA2 gene mutations using Conformation-Sensitive Gel Electrophoresis (CSGE) followed by sequencing.

Results

Sequence variations in BRCA2 gene were detected in 27 (26.4%) patients. Sixteen distinct sequence variants were detected of which 11 were (69%) in exon 11. We have identified two novel disease-causing frameshift mutations (c.4642delAA and c.4926insGACC) in two unrelated patients. Apart from this, fourteen distinct sequence variants were detected in 25 breast/ovarian cancer patients of which 8 (57%) were also novel. These include nine missense mutations, one silent mutation, one-nonsense mutation and three intronic variants.

Conclusions

The results of this study suggest that germline mutations of BRCA2 gene account for rather small proportion of Hereditary Breast/Ovarian cancer in Kerala, South India.
Literature
Bignell G, Micklem G, Stratton MR, Ashworth A, Wooster R (1997) The BRC repeats are conserved in mammalian BRCA2 proteins. Hum Mol Genet 6:53–58PubMedCrossRef
Chen J, Hedman MZ, Arver BW, Sigurdsson S, Eyfjord JE, Lindblom A (1998) BRCA2 germline mutations in Swedish breast cancer families. Eur J Hum Genet 6:134–139PubMedCrossRef
Claes K, Poppe B, Coene I, Paepe AD, Messiaen L (2004) BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families. Br J Cancer 90:1244–1251PubMedCrossRef
de la Hoya M, Osorio A, Godino J, Sulleiro S, Tosar A, Perez-Segura P, Fernandez C, Rodriguez R, Diaz-Rubio E, Benitez J, Devilee P, Caldes T (2002) Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: implications for genetic testing. Int J Cancer 97:466–471CrossRef
Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Zelada-Hedman M (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families The Breast Cancer Linkage Consortium. Am J Hum Genet 62:676–689PubMedCrossRef
Frank TS, Manley SA, Olopade OI, Cummings S, Garber JE, Bernhardt B, Antman K, Russo D, Wood ME, Mullineau L, Isaacs C, Peshkin B, Buys S, Venne V, Rowley PT, Loader S, Offit K, Robson M, Hampel H, Brener D, Winer EP, Clark S, Weber B, Strong LC, Thomas A (1998) Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 16:2417–2425PubMed
Friedman LS, Gayther SA, Kurosaki T, Gordon D, Noble B, Casey G, Ponder BA, Anton-Culver H (1997) Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population. Am J Hum Genet 60:313–319PubMed
Ganguly A, Rock MJ, Prockop DJ (1993) Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes. Proc Natl Acad Sci USA 90:10325–10329PubMedCrossRef
Gauthier-Villars M, Gad S, Caux V, Pages S, Blandy C, Stoppa-Lyonnet D (1999) Genetic testing for breast cancer predisposition. Surg Clin North Am 79:1171–87, xxiPubMedCrossRef
Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BA, Stratton MR, Easton D (1997) Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet 15:103–105PubMedCrossRef
Hamann U, Liu X, Lange S, Ulmer HU, Benner A, Scott RJ (2002) Contribution of BRCA2 germline mutations to hereditary breast/ovarian cancer in Germany. J Med Genet 39:E12PubMedCrossRef
Ikeda N, Miyoshi Y, Yoneda K, Shiba E, Sekihara Y, Kinoshita M, Noguchi S (2001) Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Int J Cancer 91:83–88PubMedCrossRef
Khoo US, Chan KY, Cheung AN, Xue WC, Shen DH, Fung KY, Ngan HY, Choy KW, Pang CP, Poon CS, Poon AY, Ozcelik H (2002) Recurrent BRCA1 and BRCA2 germline mutations in ovarian cancer: a founder mutation of BRCA1 identified in the Chinese population. Hum Mutat 19:307–308PubMedCrossRef
Loman N, Johannsson O, Kristoffersson U, Olsson H, Borg A (2001) Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. J Natl Cancer Inst 93:1215–1223PubMedCrossRef
Mazoyer S, Dunning AM, Serova O, Dearden J, Puget N, Healey CS, Gayther SA, Mangion J, Stratton MR, Lynch HT, Goldgar DE, Ponder BA, Lenoir GM (1996) A polymorphic stop codon in BRCA2. Nat Genet 14:253–254PubMedCrossRef
Peelen T, van Vliet M, Bosch A, Bignell G, Vasen HF, Klijn JG, Meijers-Heijboer H, Stratton M, van Ommen GJ, Cornelisse CJ, Devilee P (2000) Screening for BRCA2 mutations in 81 Dutch breast–ovarian cancer families. Br J Cancer 82:151–156PubMedCrossRef
Peixoto A, Salgueiro N, Santos C, Varzim G, Rocha P, Soares MJ, Pereira D, Rodrigues H, Bento MJ, Fraguas A, Moura G, Regateiro F, Castedo S, Teixeira MR (2006) BRCA1 and BRCA2 germline mutational spectrum and evidence for genetic anticipation in Portuguese breast/ovarian cancer families. Fam Cancer [Epub ahead of print]
Rahman N, Stratton MR (1998) The genetics of breast cancer susceptibility. Annu Rev Genet 32:95–121PubMedCrossRef
Rajkumar T, Soumittra N, Nancy NK, Swaminathan R, Sridevi V, Shanta V (2003) BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India. Asian Pac J Cancer Prev 4:203–208PubMed
Salazar R, Cruz-Hernandez JJ, Sanchez-Valdivieso E, Rodriguez CA, Gomez-Bernal A, Barco E, Fonseca E, Portugal T, Gonzalez-Sarmiento R (2006) BRCA1–2 mutations in breast cancer: identification of nine new variants of BRCA1–2 genes in a population from central Western Spain. Cancer Lett 233:172–177PubMedCrossRef
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
Saxena S, Szabo CI, Chopin S, Barjhoux L, Sinilnikova O, Lenoir G, Goldgar DE, Bhatanager D (2002) BRCA1 and BRCA2 in Indian breast cancer patients. Hum Mutat 20:473–474PubMedCrossRef
Saxena S, Chakraborty A, Kaushal M, Kotwal S, Bhatanager D, Mohil RS, Chintamani C, Aggarwal AK, Sharma VK, Sharma PC, Lenoir G, Goldgar DE, Szabo CI (2006) Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India. BMC Med Genet 7:75PubMedCrossRef
Shih HA, Couch FJ, Nathanson KL, Blackwood MA, Rebbeck TR, Armstrong KA, Calzone K, Stopfer J, Seal S, Stratton MR, Weber BL (2002) BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic. J Clin Oncol 20:994–999PubMedCrossRef
Syrjakoski K, Vahteristo P, Eerola H, Tamminen A, Kivinummi K, Sarantaus L, Holli K, Blomqvist C, Kallioniemi OP, Kainu T, Nevanlinna H (2000) Population-based study of BRCA1 and BRCA2 mutations in 1035 unselected Finnish breast cancer patients. J Natl Cancer Inst 92:1529–1531PubMedCrossRef
Thompson D, Easton D (2001) Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 68:410–419PubMedCrossRef
Thorlacius S, Struewing JP, Hartge P, Olafsdottir GH, Sigvaldason H, Tryggvadottir L, Wacholder S, Tulinius H, Eyfjord JE (1998) Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 352:1337–1339PubMedCrossRef
Valarmathi MT, Sawhney M, Deo SS, Shukla NK, Das SN (2004) Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and breast–ovarian cancer families. Hum Mutat 23:205PubMedCrossRef
Wagner TM, Hirtenlehner K, Shen P, Moeslinger R, Muhr D, Fleischmann E, Concin H, Doeller W, Haid A, Lang AH, Mayer P, Petru E, Ropp E, Langbauer G, Kubista E, Scheiner O, Underhill P, Mountain J, Stierer M, Zielinski C, Oefner P (1999) Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations. Hum Mol Genet 8:413–423PubMedCrossRef
Wong AK, Pero R, Ormonde PA, Tavtigian SV, Bartel PL (1997) RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J Biol Chem 272:31941–31944PubMedCrossRef
Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265:2088–2090PubMedCrossRef
Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792PubMedCrossRef
Yazici H, Bitisik O, Akisik E, Cabioglu N, Saip P, Muslumanoglu M, Glendon G, Bengisu E, Ozbilen S, Dincer M, Turkmen S, Andrulis IL, Dalay N, Ozcelik H (2000) BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients. Br J Cancer 83:737–742PubMedCrossRef
Zhi X, Szabo C, Chopin S, Suter N, Wang QS, Ostrander EA, Sinilnikova OM, Lenoir GM, Goldgar D, Shi YR (2002) BRCA1 and BRCA2 sequence variants in Chinese breast cancer families. Hum Mutat 20:474PubMedCrossRef
Metadata
Title
Novel germline mutations in BRCA2 gene among 96 hereditary breast and breast–ovarian cancer families from Kerala, South India
Authors
Vani Syamala
Leelakumari Sreeja
Volga S. Syamala
B. Vinodkumar
Praveenkumar B. Raveendran
Hariharan Sreedharan
Ratheesan Kuttappan
Lekshmi Balakrishnan
Ravindran Ankathil
Publication date
01-11-2007
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 11/2007
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-007-0229-6

Other articles of this Issue 11/2007

Journal of Cancer Research and Clinical Oncology 11/2007 Go to the issue

Original Paper

Highly aggressive behavior of malignant rhabdoid tumor: a special reference to SMARCB1/INI1 gene alterations using molecular genetic analysis including quantitative real-time PCR

Original Paper

CXCL5 overexpression is associated with late stage gastric cancer

Original Paper

Histone deacetylase inhibitors induce cell death and enhance the apoptosis-inducing activity of TRAIL in Ewing’s sarcoma cells

Original Paper

Predictive value of multidrug resistance proteins and cellular drug resistance in childhood relapsed acute lymphoblastic leukemia

Review

The Epstein Barr virus DNA levels as a tumor marker in EBV-associated cancers

Review

Protein kinase C family: On the crossroads of cell signaling in skin and tumor epithelium
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits