{"title":"全外显子组序列分析同一病例中的胃型宫颈腺癌和邻近的叶状宫颈内腺体增生症","authors":"Tsutomu Miyamoto, Koichi Ida, Yasuhiro Tanaka, Shiho Asaka, Tanri Shiozawa","doi":"10.1097/PGP.0000000000001052","DOIUrl":null,"url":null,"abstract":"<p><p>Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS, indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Whole-exome Sequence Analysis of Gastric-type Adenocarcinoma of the Uterine Cervix and Adjacent Lobular Endocervical Glandular Hyperplasia in the Same Case.\",\"authors\":\"Tsutomu Miyamoto, Koichi Ida, Yasuhiro Tanaka, Shiho Asaka, Tanri Shiozawa\",\"doi\":\"10.1097/PGP.0000000000001052\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS, indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics.</p>\",\"PeriodicalId\":14001,\"journal\":{\"name\":\"International Journal of Gynecological Pathology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Gynecological Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/PGP.0000000000001052\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Gynecological Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/PGP.0000000000001052","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
叶状宫颈内膜腺体增生(LEGH)可能是子宫颈胃型腺癌(GAS)的前驱病变。然而,其致癌的遗传机制仍不清楚。为了阐明从 LEGH 到 GAS 的致癌过程,我们比较了同一病例中早期 GAS 和邻近 LEGH 的基因突变情况。我们从一名接受子宫切除术的 IB3 期 GAS 和邻近 LEGH 患者身上获取了新鲜冷冻的组织切片。我们使用激光显微切割技术,从这些切片中分别提取了LEGH和GAS部分,并提取了基因组DNA。以正常子宫肌层的DNA为参考序列,利用全外显子测序技术进行体细胞变异分析。在LEGH和GAS中分别有61个和125个位置检测到涉及氨基酸置换的体细胞变异。两种病变中常见的变异有7个,其中致病变异只有GNAS(c.2531G>A,p.R844H),这是一种在胰腺癌和结直肠癌中经常报道的变异。LEGH没有其他致病变体;GAS的另一个致病变体仅在与GNAS相同的氨基酸位点上发现(c.2530C>T,p.R844C)。在本病例中,LEGH 和 GAS 具有相同的 GNAS 致病变体,表明这两种病变具有共同的起源。此外,目前的研究结果表明,第二个GNAS变体与LEGH发展为GAS有关。要阐明GAS的发病机制和生物学特征,还需要进一步的研究。
Whole-exome Sequence Analysis of Gastric-type Adenocarcinoma of the Uterine Cervix and Adjacent Lobular Endocervical Glandular Hyperplasia in the Same Case.
Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS, indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics.
期刊介绍:
International Journal of Gynecological Pathology is the official journal of the International Society of Gynecological Pathologists (ISGyP), and provides complete and timely coverage of advances in the understanding and management of gynecological disease. Emphasis is placed on investigations in the field of anatomic pathology. Articles devoted to experimental or animal pathology clearly relevant to an understanding of human disease are published, as are pathological and clinicopathological studies and individual case reports that offer new insights.