A. S. Khoo

L. Volpi

P. Balraj

S. Nair

AIR Universita degli studi di Milano

HUMAN MUTATION Mutation and Polymorphism Report #110 (2000) OnlineMutation and Polymorphism ReportAuthors: A.S.B. Khoo1,  P. Balraj1, L. Volpi1, and S.Nair2Affiliations:  1Division of Molecular Pathology, Institute for Medical Research, 50588 Kuala Lumpur,Malaysia; 2Division of Surgery, Kuala Lumpur Hospital, Kuala Lumpur, MalaysiaCorresponding Author Address and E-mail:Alan Khoo, Division of Molecular Pathology, Institute forMedical Research, Jalan Pahang, 50588 Kuala Lumpur,Malaysia; Tel:  (603)-4402421/4402423; Fax: (603)-2934114; E-mail:  alankhoo@imr.gov.myTitle : A new BRCA1 germline mutation (E879X) in a Malaysian breast cancer patient of Chinese descentKeywords: BRCA1, breast cancer, Malaysian ChineseSpecies: HumanChange is: MutationGene/LocusName: breast cancer 1, early onsetSymbol: BRCA1Genbank accession number: L78833OMIM accession number: 113705Locus specific database: Breast Cancer Information Core, BIChttp://www.nhgri.nih.gov/Intramural_research/Lab_transfer/ Bic/Chromosomal location: 17q12-24Inheritance: autosomal dominantMutation / polymorphism nameNucleotide change-Systematic name:c.2754G>TAmino acid change-Trivial name: E879XMutation / polymorphism type: nonsensePolymorphism frequency:Detection method: direct sequencingDetection conditions: Forward primer: 5'-acagtcgggaaacaagcatagaa-3' Reverse primer:  5'-tttggcattatcaactggcttatc-3' Standard 30 cycle PCR, annealingtemperature 60 CDiagnosis method developed: Mutation disrupts normal MboII restriction siteEvidence for existence and effect of mutation:Yes No Don’t know1. Base change found on repeat PCR sample X2. Base change segregates or appears with trait X3. Base change affects conserved residue X4. Expression analysis supports hypothesis for causation X5. Normals tested (50 required) XAncillary data1. Haplotype association :2. Ethnic background/Population association : Chinese ethnic group3. Geographic association : Malaysia4. Frequency (of mutation) in population:5. Clinical phenotype of proband : Unilateral breast cancer at age of 58 years6. Homologous allele (if recessive trait):7. PIC: (if microsatellite)HUMAN MUTATION Mutation and Polymorphism Report #110 (2000) Online8. Other:9. Present in HGMD listing:(http://www.cf.ac.uk/uwcm/mg/hgmd0.html)Yes: No: XCommentsInformation on BRCA1 mutations in non-Caucasians is lacking (Szabo and King, 1997).  Our patientwas a 58 year old postmenopausal nulliparous woman of Malaysian Chinese descent who presented withgrade III infiltrating ductal carcinoma (T3 N0 M0) of her left breast.  The tumor was negative for estrogenreceptor by immunohistochemistry but strongly positive for c-erbB-2 and p53.  The patient underwentmastectomy  with axillary clearance, local radiotherapy, adjuvant chemotherapy and tamoxifen.  She hadno known family history of breast cancer.   Her sister had been diagnosed with cervical cancer about 2decades previous, while her paternal grandmother died from an abdominal tumor (details not known).Direct sequencing of the entire BRCA1 coding region (Miki et al., 1994) of our patient showed that shewas heterozygous for a polymorphism  c.2685T>C (Y856H) (Tang et al., 1999) and a novel mutation,c.2754G>T(E879X)  both of which were in exon 11.  The mutation is predicted to result in the lost of theC-terminal region (Monteiro et al., 1996).AcknowledgmentsSupported by grant from the Ministry of Science, Technology and Environment IRPA Grant No:  06-05-01-0045.  The project was approved by the ethical committee.  The authors thank the Director of theInstitute for Medical Research for permission to publish the findings and Hisham A,  Kaur B, Lim GCC,Chia KP, Lily M, MakJW, Duraisamy G, Tan SK and Lim PKC for their support.ReferencesMiki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S et al. 1994. A strongcandidate for the breast and ovarian cancer susceptibility gene BRCA1.  Science; 266:66-71.Monteiro  AN, August A, Hanafusa H. 1996. Evidence for a transcriptional activation function ofBRCA1 C-terminal region.  Proc Natl Acad Sci USA; 93 :13595-13599.Szabo CI, King MC. 1997. Population genetics of BRCA1 and BRCA2.  Am J Hum Genet;  60: 1013-1020.Tang NLS, Pang CP, Yeo W, Choy KW, Lam PK, Suen M, Law LK, King WWK, Johnson P, Hjelm M.1999. Prevalence of mutations in BRCA1 gene among Chinese patients with breast cancer.  J. Natl.Cancer Inst.; 91:882-8855.

A new BRCA1 germline mutation (E879X) in a Malaysian breast cancer patient of Chinese descent

https://air.unimi.it/retrieve/handle/2434/200472/224707/Khoo%20et%20al%202000%20Hum%20Mut.pdf

A new BRCA1 germline mutation (E879X) in a Malaysian breast cancer patient of Chinese descent

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