Pakkanen Sanna, Wahlfors Tiina, Siltanen Sanna, Patrikainen Mimmi, Matikainen Mika P, Tammela Teuvo L J, Schleutker Johanna
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
J Negat Results Biomed. 2009 Dec 15;8:12. doi: 10.1186/1477-5751-8-12.
PALB2 1592delT mutation is associated with increased breast cancer and suggestive prostate cancer (PRCA) risk in Finland. In this study we wanted to assess if any other PALB2 variants associate to increased PRCA risk and clinically describe patients with formerly found PALB2 1592delT mutation.
Finnish families with two or more PRCA cases (n = 178) and unselected cases (n = 285) with complete clinical data were initially screened for variants in the coding region and splice sites of PALB2. Potentially interesting variants were verified in additional set of unselected cases (n = 463).
From our clinically defined sample set we identified total of six variants in PALB2. No novel variants among Finnish PRCA cases were found. Clinical characteristics of the variant carriers, including the previously described family carrying PALB2 1592delT, revealed a trend towards aggressive disease, which also applied to a few non-familial cases. Hypersensitivity to mitomycin C (MMC) of lymphoblasts from individuals from the family with 1592delT revealed haploinsufficiency among carriers with altered genotype.
Though any of the detected PALB2 variants do not associate to PRCA in population level in Finland it cannot be ruled out that some of these variants contribute to cancer susceptibility at individual level.
在芬兰，PALB2基因1592delT突变与乳腺癌风险增加以及前列腺癌（PRCA）风险升高有关。在本研究中，我们想评估是否有其他PALB2变异与PRCA风险增加相关，并对先前发现携带PALB2 1592delT突变的患者进行临床描述。
对有两例或更多PRCA病例的芬兰家族（n = 178）以及具有完整临床数据的未选择病例（n = 285），最初筛查PALB2编码区和剪接位点的变异。在另一组未选择病例（n = 463）中验证潜在有趣的变异。
从我们临床定义的样本集中，我们在PALB2中总共鉴定出六个变异。在芬兰PRCA病例中未发现新的变异。变异携带者的临床特征，包括先前描述的携带PALB2 1592delT的家族，显示出疾病侵袭性的趋势，这也适用于一些非家族性病例。对来自携带1592delT家族个体的淋巴细胞进行丝裂霉素C（MMC）敏感性检测，发现基因型改变的携带者存在单倍体不足。
虽然在芬兰人群水平上，任何检测到的PALB2变异都与PRCA无关，但不能排除其中一些变异在个体水平上对癌症易感性有影响。
