Uemura Sunao, Matsubayashi Hiroyuki, Kiyozumi Yoshimi, Uesaka Katsuhiko, Yamamoto Yusuke, Sasaki Keiko, Abe Masato, Urakami Kenichi, Kusuhara Masatoshi, Yamaguchi Ken
Division of Pathology, Shizuoka Cancer Center, Suntogun, Nagaizumi, Shizuoka, 411-8777, Japan.
Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Suntogun, Nagaizumi, Shizuoka, 411-8777, Japan.
Fam Cancer. 2018 Apr;17(2):255-259. doi: 10.1007/s10689-017-0025-7.
A minor fraction of pancreatic ductal adenocarcinoma (PDAC) develops in association with germline mutations of the genes responsible for inherited cancer syndromes. However, the PDAC that has a germline PTEN mutation has not received much attention. Genome-wide whole exome sequencing was performed on germline and somatic DNA from an 82-year-old woman who had developed a solid pancreatic cancer but did not show characteristic findings of PTEN hamartoma tumor syndromes (PHTS). Histology of the resected pancreatic tumor showed unique PDAC findings of primarily dendriform structures and dense fibrous tissue, accompanied by multiple pancreatic intraepithelial neoplasias in the vicinity. The tumor immunohistochemistry revealed a loss of PTEN expression and overexpression of TP53. Exome sequencing revealed a K-ras mutation (p.Gly12Val). Germline exome sequencing revealed a missense mutation of PTEN (p.Arg234Gln), a rare variant with a reported association with cancer development but not with other PHTS phenotypes. To our knowledge, this is the first report of PDAC associated with a germline PTEN mutation, particularly a rare variant (p.Arg234Gln) with cancer risks.
一小部分胰腺导管腺癌（PDAC）与遗传性癌症综合征相关基因的种系突变有关。然而，具有种系PTEN突变的PDAC尚未受到太多关注。对一名82岁患实性胰腺癌但未表现出PTEN错构瘤肿瘤综合征（PHTS）特征性表现的女性的种系和体细胞DNA进行了全基因组外显子组测序。切除的胰腺肿瘤组织学显示出独特的PDAC表现，主要为树枝状结构和致密纤维组织，附近伴有多个胰腺上皮内瘤变。肿瘤免疫组化显示PTEN表达缺失和TP53过表达。外显子组测序显示存在K-ras突变（p.Gly12Val）。种系外显子组测序显示PTEN存在错义突变（p.Arg234Gln），这是一种罕见变异，有报道称其与癌症发生有关，但与其他PHTS表型无关。据我们所知，这是首例与种系PTEN突变相关的PDAC报道，尤其是与癌症风险相关的罕见变异（p.Arg234Gln）。
