Francies F Z, Wainstein T, De Leeneer K, Cairns A, Murdoch M, Nietz S, Cubasch H, Poppe B, Van Maerken T, Crombez B, Coene I, Kerr R, Slabbert J P, Vral A, Krause A, Baeyens A, Claes K B M
iThemba LABS-National Research Foundation, Somerset West, South Africa.
Department of Radiation Sciences, University of the Witwatersrand, Johannesburg, South Africa.
BMC Cancer. 2015 Nov 17;15:912. doi: 10.1186/s12885-015-1913-6.
Current knowledge of the aetiology of hereditary breast cancer in the four main South African population groups (black, coloured, Indian and white) is limited. Risk assessments in the black, coloured and Indian population groups are challenging because of restricted information regarding the underlying genetic contributions to inherited breast cancer in these populations. We focused this study on premenopausal patients (diagnosed with breast cancer before the age of 50; n = 78) and triple negative breast cancer (TNBC) patients (n = 30) from the four South African ethnic groups. The aim of this study was to determine the frequency and spectrum of germline mutations in BRCA1, BRCA2 and PALB2 and to evaluate the presence of the CHEK2 c.1100delC allele in these patients.
In total, 108 South African breast cancer patients underwent mutation screening using a Next-Generation Sequencing (NGS) approach in combination with Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large rearrangements in BRCA1 and BRCA2.
In 13 (12 %) patients a deleterious mutation in BRCA1/2 was detected, three of which were novel mutations in black patients. None of the study participants was found to have an unequivocal pathogenic mutation in PALB2. Two (white) patients tested positive for the CHEK2 c.1100delC mutation, however, one of these also carried a deleterious BRCA2 mutation. Additionally, six variants of unknown clinical significance were identified (4 in BRCA2, 2 in PALB2), all in black patients. Within the group of TNBC patients, a higher mutation frequency was obtained (23.3 %; 7/30) than in the group of patients diagnosed before the age of 50 (7.7 %; 6/78).
This study highlights the importance of evaluating germline mutations in major breast cancer genes in all of the South African population groups. This NGS study shows that mutation analysis is warranted in South African patients with triple negative and/or in premenopausal breast cancer.
目前对于南非四个主要人群（黑人、混血人种、印度人和白人）遗传性乳腺癌病因的了解有限。由于关于这些人群中遗传性乳腺癌潜在遗传因素的信息有限，对黑人、混血人种和印度人群体进行风险评估具有挑战性。我们将这项研究聚焦于来自南非四个种族群体的绝经前患者（50岁之前被诊断为乳腺癌；n = 78）和三阴性乳腺癌（TNBC）患者（n = 30）。本研究的目的是确定BRCA1、BRCA2和PALB2种系突变的频率和谱，并评估这些患者中CHEK2 c.1100delC等位基因的存在情况。
总共108名南非乳腺癌患者采用下一代测序（NGS）方法结合多重连接依赖探针扩增（MLPA）进行突变筛查，以检测BRCA1和BRCA2中的大片段重排。
在13名（12%）患者中检测到BRCA1/2的有害突变，其中3个是黑人患者中的新突变。未发现研究参与者在PALB2中有明确的致病突变。两名（白人）患者CHEK2 c.1100delC突变检测呈阳性，然而，其中一名患者也携带有害的BRCA2突变。此外，还鉴定出6个临床意义不明的变异（BRCA2中有4个，PALB2中有2个），均在黑人患者中。在TNBC患者组中，获得的突变频率（23.3%；7/30）高于50岁之前诊断的患者组（7.7%；6/
