Background: The pathogenic/likely pathogenic (P/LP) variant detection rate and profile ofPALB2, the third most important breast cancer gene, may vary between different populations. Methods:PALB2was analyzed in peripheral blood samples of three independent cohorts: prospectively between September 2021 and March 2023 (i) in 1280 consecutive patients with breast and/or ovarian cancer (HBOC), (ii) in 568 patients with other cancers (controls), and retrospectively, (iii) in 191 young breast cancer (<33 years, yBC) patients. These data were compared with data of 134,187 non-cancer individuals retrieved from the Genome Aggregation Database. Results: Altogether, 235 cases (235/1280; 18.3%) carried at least one P/LP variant in one of the HBOC susceptibility genes. P/LPPALB2variants were identified in 18 patients (1.4%; 18/1280) in the HBOC and 3 cases (1.5%; 3/191) in the yBC group. In the control group, only one patient had a disease-causingPALB2variant (0.17%; 1/568) as a secondary finding not related to the disease, which was similar (0.15%; 205/134,187) in the non-cancer control group. The NM_024675.4:c.509_510delGA variant was the most common among our patients (33%; 6/18). We did not find a significant difference in the incidence ofPALB2disease-causing variants according to age; however, the median age of tumor onset was lower inPALB2P/LP carriers versus wild-type patients (44 vs. 48 years). In our cohort, the odds ratio for breast cancer risk in women withPALB2P/LP variants was between 8.1 and 9.3 compared to non-HBOC cancer patients and the non-cancer population, respectively. Conclusions:PALB2P/LP variants are not uncommon among breast and/or ovarian cancer patients. Their incidence was the same in the two breast cancer cohorts studied but may occur rarely in patients with non-breast/ovarian cancer. The c.509_510delGA variant is particularly common in the studied Hungarian patient population.
背景：作为第三大重要乳腺癌基因，PALB2的致病性/可能致病性（P/LP）变异检出率及其特征在不同人群中可能存在差异。方法：对三个独立队列的外周血样本进行PALB2基因分析：前瞻性研究（2021年9月至2023年3月）包括（i）1280例连续收治的遗传性乳腺癌/卵巢癌（HBOC）患者，以及（ii）568例其他癌症患者（对照组）；回顾性研究包括（iii）191例年轻乳腺癌（<33岁，yBC）患者。这些数据与从基因组聚合数据库获取的134,187名非癌症个体数据进行比较。结果：总体而言，235例（235/1280；18.3%）携带至少一种HBOC易感基因的P/LP变异。在HBOC组中发现18例患者（1.4%；18/1280）携带PALB2 P/LP变异，yBC组中检出3例（1.5%；3/191）。对照组中仅1例患者携带与疾病无关的致病性PALB2变异（0.17%；1/568），该比例与非癌症对照组（0.15%；205/134,187）相近。NM_024675.4:c.509_510delGA变异是本队列中最常见的变异类型（33%；6/18）。虽然未发现PALB2致病性变异发生率存在显著年龄差异，但携带PALB2 P/LP变异者的肿瘤发病中位年龄较野生型患者更低（44岁 vs. 48岁）。在本队列中，携带PALB2 P/LP变异女性的乳腺癌风险比值比，相较于非HBOC癌症患者和非癌症人群分别为8.1和9.3。结论：PALB2 P/LP变异在乳腺癌和/或卵巢癌患者中并不罕见。其在两个乳腺癌队列中的发生率相同，但在非乳腺/卵巢癌患者中可能极少发生。c.509_510delGA变异在研究的匈牙利患者群体中尤为常见。
PALB2Variants Extend the Mutational Profile of Hungarian Patients with Breast and Ovarian Cancer
肿瘤(癌症)患者之家