Laboratoire de Recherche et de Biosécurité P3, Hôpital Militaire d'Instruction Mohammed V, Rabat, Maroc.
Unité de séquençage, Laboratoire de Virologie, Centre de Virologie, des Maladies Infectieuses et Tropicales, Hôpital Militaire d'Instruction Mohammed V, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Maroc.
BMC Cancer. 2022 Feb 25;22(1):208. doi: 10.1186/s12885-022-09181-4.
Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations.
To establish the knowledge about BRCA PVs and to determine the prevalence of the specific and recurrent/founder variants in BRCA genes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia.
Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated both BRCA1 and BRCA2 genes, four studies examined the entire coding region of the BRCA1 gene, and six studies in which the analysis was limited to a few BRCA1 and/or BRCA2 exons. Overall, 76 PVs (44 in BRCA1 and32 in BRCA2) were identified in 196 BC and/or OC patients (129 BRCA1 and 67 BRCA2 carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) in BRCA1 and 8/32 (25%) in BRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, the BRCA1 c.68_69del and BRCA1 c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex: BRCA1 c.181T>G, BRCA1 c1016dupA). The most well characterized PVs are four in BRCA1 gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total established BRCA1 PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of all BRCA1 North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants including BRCA1 3279delC, BRCA1 c.5266dup and BRCA2 c.1310_1313detAAGA was detected in 42 patients. BRCA1 founder variants explain around 36.4% (47/129) of BC and outnumber BRCA2 founder variants by a ratio of ≈3:1.
Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.
阐明 BRCA（BRCA1 和 BRCA2）基因中的特定和频发/创始变异（PVs）可以使发展中国家负担得起乳腺癌（BC）和/或卵巢癌（OC）的基因检测费用。
为了了解 BRCA PVs 的知识，并确定北非 BC 和/或 OC 女性中 BRCA 基因中特定和频发/创始变异的流行率，在摩洛哥、阿尔及利亚和突尼斯进行了系统评价。
数据库搜索产生了 25 篇相关参考文献，其中包括在摩洛哥的 11 项研究、在阿尔及利亚的 5 项研究和在突尼斯的 9 项研究。总体而言，15 项研究同时调查了 BRCA1 和 BRCA2 基因，4 项研究检查了 BRCA1 基因的整个编码区，6 项研究仅限于少数 BRCA1 和/或 BRCA2 外显子的分析。总体而言，在 196 名 BC 和/或 OC 患者（129 名 BRCA1 和 67 名 BRCA2 携带者）中鉴定出 76 个 PVs（44 个在 BRCA1 中，32 个在 BRCA2 中）。76 个 PVs 中的 18 个（23.7%）[10/44（22.7%）在 BRCA1 中，8/32（25%）在 BRCA2 中]是首次报道的，被认为是新的 PVs。在那些被认为不是北非起源的 PVs 中，BRCA1 c.68_69del 和 BRCA1 c.5266dupC 犹太创始等位基因，以及在欧洲人群中报告为频发/创始变异的 PVs（例如：BRCA1 c.181T>G、BRCA1 c1016dupA）。最具特征性的 PVs 有 4 个在 BRCA1 基因中[c.211dupA（14.7%）、c.798_799detTT（14%）、c.5266dup（8.5%）、c.5309G>T（7.8%）、c.3279delC（4.7%）]和 1 个在 BRCA2 基因中[c.1310_1313detAAGA（38.9%）]。c.211dupA 和 c.5309G>T PVs 被确定为突尼斯和摩洛哥的特定创始变异，分别占总鉴定的 BRCA1 PVs 的 35.2%（19/54）和 20.4%（10/49）。c.798_799delTT 变异在所有北非 BRCA1 携带者中占 14%（18/129），提示存在一个创始等位基因。在 42 名患者中检测到广泛的频发变异，包括 BRCA1 3279delC、BRCA1 c.5266dup 和 BRCA2 c.1310_1313detAAGA。BRCA1 创始变异解释了大约 36.4%（47/129）的 BC，BRCA2 创始变异的数量是其的 3 倍左右。
对 BC 和/或 OC 患者进行特定和频发/创始 PVs 检测可能是最具成本效益的分子诊断策略。
