دورية أكاديمية
أعرض في EDS

Targeted gene sequencing of Lynch syndrome-related and sporadic endometrial carcinomas.

التفاصيل البيبلوغرافية
العنوان: Targeted gene sequencing of Lynch syndrome-related and sporadic endometrial carcinomas.
المؤلفون: Libera L; Unit of Pathology, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy., Craparotta I; IRCCS Institute for Pharmacological Researches Mario Negri, Department of Oncology, 20156, Milano, Italy., Sahnane N; Unit of Pathology, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy; Research Center for the study of Hereditary and Familial Tumors, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy. Electronic address: n.sahnane@gmail.com., Chiaravalli AM; Research Center for the study of Hereditary and Familial Tumors, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy; Unit of Pathology, ASST-Sette Laghi, 21100, Varese, Italy., Mannarino L; IRCCS Institute for Pharmacological Researches Mario Negri, Department of Oncology, 20156, Milano, Italy., Cerutti R; Unit of Pathology, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy; Research Center for the study of Hereditary and Familial Tumors, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy., Riva C; Unit of Pathology, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy; Research Center for the study of Hereditary and Familial Tumors, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy., Marchini S; IRCCS Institute for Pharmacological Researches Mario Negri, Department of Oncology, 20156, Milano, Italy., Furlan D; Unit of Pathology, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy; Research Center for the study of Hereditary and Familial Tumors, Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy.
المصدر: Human pathology [Hum Pathol] 2018 Nov; Vol. 81, pp. 235-244. Date of Electronic Publication: 2018 Jul 03.
نوع المنشور: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: W B Saunders Country of Publication: United States NLM ID: 9421547 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-8392 (Electronic) Linking ISSN: 00468177 NLM ISO Abbreviation: Hum Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: Philadelphia, PA : W B Saunders
Original Publication: Philadelphia, W B. Saunders Co.
مواضيع طبية MeSH: High-Throughput Nucleotide Sequencing* , Microsatellite Instability* , Mutation*, Base Pair Mismatch/*genetics , Biomarkers, Tumor/*genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics , DNA Mutational Analysis/*methods , Endometrial Neoplasms/*genetics , Gene Expression Profiling/*methods, Adult ; Aged ; Colorectal Neoplasms, Hereditary Nonpolyposis/pathology ; DNA-Binding Proteins ; Endometrial Neoplasms/pathology ; Female ; Gene Silencing ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Middle Aged ; MutL Protein Homolog 1/genetics ; Nuclear Proteins/genetics ; Phenotype ; Predictive Value of Tests ; Proto-Oncogene Proteins p21(ras)/genetics ; Transcription Factors/genetics
مستخلص: About one-third of endometrial carcinomas (ECs), mainly of endometrioid histology, harbor the mismatch repair (MMR) defects and microsatellite instability (MSI). Among these, ECs arising in women with Lynch syndrome (LS) account for a large proportion. To date, no somatic genetic analyses have been published comparing LS-ECs with sporadic ECs. In this work, we examined the mutational profiles of a well-characterized series of sporadic and LS-related ECs, performing exonic targeted sequencing of 16 genes mainly involved in MSI ECs. Next-generation sequencing analysis was performed in 35 ECs on the MiSeq platform (Illumina, San Diego, CA), and the mutational profile was analyzed integrating molecular and immunohistochemical data. PTEN, ARID1A, and ARID2 were the most frequently mutated genes regardless of MSI status or family history. MSI ECs showed a higher mutational load than MMR-proficient cases, exhibiting an MMR-deficient mutational signature. Among MSI tumors, LS-related and sporadic ECs exhibited similar mutational profiles, with MSH2 as the most commonly mutated gene. KRAS mutations seemed to be more common in sporadic MSI ECs than in LS-related ECs even if further studies are needed to confirm this finding. MMR-deficient ECs carried a higher mutational load and an excess of C>T transitions compared with MMR-proficient ECs, suggesting that the use of a small gene panel may be adequate to highlight significant differences between these 2 groups. An integrated analysis of genetic and epigenetic features of LS-related and sporadic ECs provides useful insights into disease biology and diagnostic classification of these tumors.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: ARID1A; Endometrial cancer; Lynch syndrome; MLH1 silencing; MMR defect; Targeted sequencing
المشرفين على المادة: 0 (ARID1A protein, human)
0 (Biomarkers, Tumor)
0 (DNA-Binding Proteins)
0 (KRAS protein, human)
0 (MLH1 protein, human)
0 (Nuclear Proteins)
0 (Transcription Factors)
EC 3.6.1.3 (MutL Protein Homolog 1)
EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
تواريخ الأحداث: Date Created: 20181114 Date Completed: 20191022 Latest Revision: 20201209
رمز التحديث: 20231215
DOI: 10.1016/j.humpath.2018.06.029
PMID: 30420047
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-8392
DOI:10.1016/j.humpath.2018.06.029