Clinical and genetic analysis of 18 pancreatic carcinoma/melanoma-prone families
Clinical and genetic analysis of 18 pancreatic carcinoma/melanoma-prone families
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DOI：
10.1111/j.1399-0004.2009.01352.x
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发表时间：
2010-04-01
影响因子：
3.5
通讯作者：
Slater, E. P.
中科院分区：
文献类型：
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作者：
Bartsch, D. K.;Langer, P.;Slater, E. P.
同时患有黑色素瘤和胰腺癌的家族极为罕见，有些家族患有常染色体显性遗传的家族性非典型多发性痣黑色素瘤-胰腺癌 (FAMMM-PC) 综合征。这种胰腺癌-黑色素瘤易感家族的表型和基因型表达尚不明确。德国 Krebshilfe 国家家族性胰腺癌病例集包括 110 个胰腺癌家族，其中 18 个家族 (16%) 显示胰腺癌与黑色素瘤相关。对这 18 个家族的表型以及候选基因 CDKN2A、BRCA2、CHEK2、NOD2、ARL11 和 Palladin (PALD) 种系突变的患病率进行了分析。有两种类型的家族：5 个具有 FAMMM-PC 表型的家族和 13 个不具有多痣表型 (PCMS) 的 PC/黑色素瘤家族。两类家庭中 PC 和黑色素瘤的患病率相似。 PCMS 中其他肿瘤类型（尤其是乳腺癌）的患病率 (11%) 高于 FAMMM-PC 家族中的患病率 (2.4%，p = 0.02)。在 18 个 PCMS 家族中的 2 个 (11%) 中发现了 CDKN2A 突变。在一个没有乳腺癌的 PCMS 家族中检测到了共分离的 BRCA2 突变。在这两种类型的家族中均未检测到已报道的 NOD2、Palladin、ARL11 或 CHEK2 基因种系突变。总之，PC 和黑色素瘤积累的家族表现出多种表型表达，这并不总是与 FAMMM-PC 表型一致。需要分析更多的 PC/黑色素瘤倾向家族，以澄清这些家族是否代表 FAMMM-PC 综合征的变异或两种不同的遗传性癌症综合征。
Families with both melanoma and pancreatic cancer are extremely rare and some are affected with the autosomal dominant inherited familial atypical multiple mole melanoma-pancreatic cancer (FAMMM-PC) syndrome. The phenotypic and genotypic expressions of such pancreatic cancer-melanoma prone families are not well defined. The National Case Collection of Familial Pancreatic Cancer of the Deutsche Krebshilfe includes 110 pancreatic cancer families, 18 of which (16%) show an association of pancreatic cancer and melanoma. These 18 families were analysed regarding their phenotype and the prevalence of germline mutations in the candidate genes CDKN2A, BRCA2, CHEK2, NOD2, ARL11 and Palladin (PALLD). There were two types of families: five families with the FAMMM-PC phenotype and 13 PC/melanoma families without the multiple mole phenotypes (PCMS). The prevalences of PC and melanoma in the two types of families were similar. The prevalence of other tumour types, especially breast carcinoma, was higher (11%) in PCMS- than in FAMMM-PC families (2.4%, p = 0.02). CDKN2A mutations were identified in 2 of 18 (11%) PCMS families. A cosegregating BRCA2 mutation was detected in one PCMS family without breast cancer. None of the reported germline mutations in the NOD2, Palladin, ARL11 or CHEK2 genes were detected in either type of family. In conclusion, families with an accumulation of PC and melanoma show a large variety of phenotypic expression, which is not always consistent with the FAMMM-PC phenotype. More PC/melanoma-prone families need to be analysed to clarify whether such families represent variations of the FAMMM-PC syndrome or two distinct hereditary cancer syndromes.