BACKGROUND: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. METHODS: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). RESULTS: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients. CONCLUSION: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.
BACKGROUND: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. METHODS: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancerpatients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancerpatients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). RESULTS: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancerpatients. CONCLUSION: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancerpatients.
Authors: Timothy R Rebbeck; Tara M Friebel; Eitan Friedman; Ute Hamann; Dezheng Huo; Ava Kwong; Edith Olah; Olufunmilayo I Olopade; Angela R Solano; Soo-Hwang Teo; Mads Thomassen; Jeffrey N Weitzel; T L Chan; Fergus J Couch; David E Goldgar; Torben A Kruse; Edenir Inêz Palmero; Sue Kyung Park; Diana Torres; Elizabeth J van Rensburg; Lesley McGuffog; Michael T Parsons; Goska Leslie; Cora M Aalfs; Julio Abugattas; Julian Adlard; Simona Agata; Kristiina Aittomäki; Lesley Andrews; Irene L Andrulis; Adalgeir Arason; Norbert Arnold; Banu K Arun; Ella Asseryanis; Leo Auerbach; Jacopo Azzollini; Judith Balmaña; Monica Barile; Rosa B Barkardottir; Daniel Barrowdale; Javier Benitez; Andreas Berger; Raanan Berger; Amie M Blanco; Kathleen R Blazer; Marinus J Blok; Valérie Bonadona; Bernardo Bonanni; Angela R Bradbury; Carole Brewer; Bruno Buecher; Saundra S Buys; Trinidad Caldes; Almuth Caliebe; Maria A Caligo; Ian Campbell; Sandrine M Caputo; Jocelyne Chiquette; Wendy K Chung; Kathleen B M Claes; J Margriet Collée; Jackie Cook; Rosemarie Davidson; Miguel de la Hoya; Kim De Leeneer; Antoine de Pauw; Capucine Delnatte; Orland Diez; Yuan Chun Ding; Nina Ditsch; Susan M Domchek; Cecilia M Dorfling; Carolina Velazquez; Bernd Dworniczak; Jacqueline Eason; Douglas F Easton; Ros Eeles; Hans Ehrencrona; Bent Ejlertsen; Christoph Engel; Stefanie Engert; D Gareth Evans; Laurence Faivre; Lidia Feliubadaló; Sandra Fert Ferrer; Lenka Foretova; Jeffrey Fowler; Debra Frost; Henrique C R Galvão; Patricia A Ganz; Judy Garber; Marion Gauthier-Villars; Andrea Gehrig; Anne-Marie Gerdes; Paul Gesta; Giuseppe Giannini; Sophie Giraud; Gord Glendon; Andrew K Godwin; Mark H Greene; Jacek Gronwald; Angelica Gutierrez-Barrera; Eric Hahnen; Jan Hauke; Alex Henderson; Julia Hentschel; Frans B L Hogervorst; Ellen Honisch; Evgeny N Imyanitov; Claudine Isaacs; Louise Izatt; Angel Izquierdo; Anna Jakubowska; Paul James; Ramunas Janavicius; Uffe Birk Jensen; Esther M John; Joseph Vijai; Katarzyna Kaczmarek; Beth Y Karlan; Karin Kast; KConFab Investigators; Sung-Won Kim; Irene Konstantopoulou; Jacob Korach; Yael Laitman; Adriana Lasa; Christine Lasset; Conxi Lázaro; Annette Lee; Min Hyuk Lee; Jenny Lester; Fabienne Lesueur; Annelie Liljegren; Noralane M Lindor; Michel Longy; Jennifer T Loud; Karen H Lu; Jan Lubinski; Eva Machackova; Siranoush Manoukian; Véronique Mari; Cristina Martínez-Bouzas; Zoltan Matrai; Noura Mebirouk; Hanne E J Meijers-Heijboer; Alfons Meindl; Arjen R Mensenkamp; Ugnius Mickys; Austin Miller; Marco Montagna; Kirsten B Moysich; Anna Marie Mulligan; Jacob Musinsky; Susan L Neuhausen; Heli Nevanlinna; Joanne Ngeow; Huu Phuc Nguyen; Dieter Niederacher; Henriette Roed Nielsen; Finn Cilius Nielsen; Robert L Nussbaum; Kenneth Offit; Anna Öfverholm; Kai-Ren Ong; Ana Osorio; Laura Papi; Janos Papp; Barbara Pasini; Inge Sokilde Pedersen; Ana Peixoto; Nina Peruga; Paolo Peterlongo; Esther Pohl; Nisha Pradhan; Karolina Prajzendanc; Fabienne Prieur; Pascal Pujol; Paolo Radice; Susan J Ramus; Johanna Rantala; Muhammad Usman Rashid; Kerstin Rhiem; Mark Robson; Gustavo C Rodriguez; Mark T Rogers; Vilius Rudaitis; Ane Y Schmidt; Rita Katharina Schmutzler; Leigha Senter; Payal D Shah; Priyanka Sharma; Lucy E Side; Jacques Simard; Christian F Singer; Anne-Bine Skytte; Thomas P Slavin; Katie Snape; Hagay Sobol; Melissa Southey; Linda Steele; Doris Steinemann; Grzegorz Sukiennicki; Christian Sutter; Csilla I Szabo; Yen Y Tan; Manuel R Teixeira; Mary Beth Terry; Alex Teulé; Abigail Thomas; Darcy L Thull; Marc Tischkowitz; Silvia Tognazzo; Amanda Ewart Toland; Sabine Topka; Alison H Trainer; Nadine Tung; Christi J van Asperen; Annemieke H van der Hout; Lizet E van der Kolk; Rob B van der Luijt; Mattias Van Heetvelde; Liliana Varesco; Raymonda Varon-Mateeva; Ana Vega; Cynthia Villarreal-Garza; Anna von Wachenfeldt; Lisa Walker; Shan Wang-Gohrke; Barbara Wappenschmidt; Bernhard H F Weber; Drakoulis Yannoukakos; Sook-Yee Yoon; Cristina Zanzottera; Jamal Zidan; Kristin K Zorn; Christina G Hutten Selkirk; Peter J Hulick; Georgia Chenevix-Trench; Amanda B Spurdle; Antonis C Antoniou; Katherine L Nathanson Journal: Hum Mutat Date: 2018-03-12 Impact factor: 4.700