Woolly hair nevus caused by somatic mutation and Costello syndrome caused by germline mutation in HRAS : Consider parental mosaicism in prenatal counseling

2021 ◽  
Author(s):  
Jianying Liang ◽  
Yifeng Guo ◽  
Zhiyong Lu ◽  
Hong Yu ◽  
Liangcai Wu ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Germline Mutation ◽  
Costello Syndrome ◽  
Prenatal Counseling ◽  
Woolly Hair

Pathogenic germline mutation profile in Chinese lung cancers and related-driver mutation pattern.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13003-e13003
Author(s):  
Wenying Peng ◽  
Lin Wu ◽  
Lianpeng Chang ◽  
Jin Li ◽  
Jing Bai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Somatic Mutation ◽  
Germline Mutation ◽  
Therapy Response ◽  
Therapeutic Interventions ◽  
Onset Age ◽  
Germline Variants ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Predisposition Genes

e13003 Background: Many cancers could be driven by germline mutation exampled as BRCA1/2 in breast or ovarian cancer. However, the candidate predisposition variants for Chinese lung cancer are largely unknown. Methods: We reviewed 1797 Chinese lung cancer patients with paired tumor-normal samples sequenced by a 1021 gene panel. The annotation of germline variants within 95 selected susceptible genes was based on ACMG 2015 version guideline. Results: The frequency of patients identified with pathogenic or likely pathogenic (P/LP) germline variants were 5.95% (107 in 1797), which elevated to 10.1% (9 in 89) in patients younger than 40. Totally, 112 mutations from 35 genes were screened out. Recurrent pathogenic germline genes were BRCA2 (n = 14), FANCA (n = 9), RAD51D (n = 7), MUTYH (n = 7), ATM (n = 7) and TP53 (n = 5). The average age at diagnosis was numerically 2 years earlier in patients with P/LP (mean, 58.2 vs. 60.0, p = 0.22) than other patients without significance, but different genes contribute to discordant effects. Significantly early onset age was found in germline BRCA1/ 2 mutation (median, 52.5 versus 60.0 yrs in patients without P/LP, p = 0.0080) while later onset age was associated with germline PMS2 mutation (median, 74 versus 60.0 yrs, p = 0.0214 ). In terms of clinical actionable somatic mutation, the frequency of KRAS (15/89, 16.85% versus 121/1429, 8.47%, p = 0.012) and c-MET (6/89, 6.74% versus 31/1429, 2.17%, p = 0.018) in germline mutant patients were significantly higher, while TP53 (41/89, 46.07% versus 847/1429, 59.27%, p = 0.019) was apparently less mutated in P/LP lung cancer. As for frequency of EGFR, ALK, ROS-1, RET and BRAF, mutation frequency were not significantly different in lung cancer with germline mutation. Conclusions: Our study delineated the pathogenic germline mutation landscape in Chinese lung cancers for the first time. Predisposition genes demonstrated clinical actionable roles in onset age and therapeutic interventions. Further follow up may clarify the contribution of germline mutation to somatic mutation driven targeted therapy response and prognosis.

scholarly journals Case Report and Literature Review: Pulmonary Sclerosing Pneumocytoma With Multiple Metastases Harboring AKT1 E17K Somatic Mutation and TP53 C176Y Germline Mutation

2021 ◽  
Vol 8 ◽  
Author(s):  
Qiushi Wang ◽  
Chunlin Lu ◽  
Minrui Jiang ◽  
Mengxia Li ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Germline Mutation ◽  
Molecular Genetic ◽  
Primary Lung Cancer ◽  
Middle Lobe ◽  
Biological Behavior ◽  
Pathological Examination ◽  
Regional Lymph Nodes ◽  
Genetic Changes ◽  
Short Period

Pulmonary Sclerosing Pneumocytoma (PSP) is considered as a benign tumor, although a few cases have been reported to have multiple lesions, recurrence, and even regional lymph nodes (LNs) metastasis. Here, we report a case of PSP with atypical histologic features and malignant biological behavior, and explore its molecular genetic changes. The 23-year-old male showed a 6.5-cm pulmonary nodule in the right middle lobe (RML) and enlarged media stinal LNs. He underwent thoracoscopic RML lobectomy, systematic LNs dissection, and mediastinal lymphadenectomy. The metastases to the cervical LNs and liver were detected in a short period and then resected. Postoperative pathological examination confirmed the diagnosis of PSP in all the lesions, based on the histological characteristics and immune phenotypes. Furthermore, whole-exome sequencing identified both AKT1 E17K somatic mutation and TP53 C176Y germline mutation in this case. Thus, we presented an extremely rare case of atypical PSP with rapid recurrence and multiply metastases, which can easily be misdiagnosed as primary lung cancer. In addition, PSP-specific AKT1 E17K somatic E17K somatic mutation accompanied with TP53 C176Y germline mutation may contribute to the malignant clinical course of this tumor.

A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT

Blood ◽  
2013 ◽  
Vol 122 (7) ◽  
pp. 1312-1315 ◽  
Author(s):  
Peter M. Krawitz ◽  
Britta Höchsmann ◽  
Yoshiko Murakami ◽  
Britta Teubner ◽  
Ulrike Krüger ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Germline Mutation ◽  
Splice Site ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Second Hit ◽  
Key Points

Key Points A carrier of a deleterious splice site mutation in PIGT acquired a second hit in PIGT and developed PNH.

scholarly journals Novel genetic alteration in congenital melanocytic nevus: MAP2K1 germline mutation with BRAF somatic mutation

Hereditas ◽  
2020 ◽  
Vol 157 (1) ◽  
Author(s):  
Yun Zou ◽  
Yi Sun ◽  
Xiaojing Zeng ◽  
Yun Liu ◽  
Qingqing Cen ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Germline Mutation ◽  
Melanocytic Nevus ◽  
Genetic Alteration ◽  
Congenital Melanocytic Nevus

scholarly journals Effects of germline and somatic events in candidate BRCAness genes on breast-tumor signatures

2019 ◽  
Author(s):  
Weston R. Bodily ◽  
Brian H. Shirts ◽  
Tom Walsh ◽  
Suleyman Gulsuner ◽  
Mary-Claire King ◽  
...  
Keyword(s):  
Gene Expression ◽  
Somatic Mutation ◽  
Germline Mutation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Germline Mutations ◽  
Homozygous Deletion ◽  
The Other ◽  
High Similarity ◽  
Brca1 Brca2

AbstractBackgroundMutations in BRCA1 and BRCA2 cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR deficiency are characteristic somatic-mutation signatures and gene-expression patterns. The term “BRCAness” describes tumors that harbor an HR defect but have no detectable germline mutation in BRCA1 or BRCA2. A better understanding of the genes and molecular events associated with BRCAness could provide mechanistic insights and guide development of targeted treatments.MethodsUsing data from The Cancer Genome Atlas (TCGA) for 1101 breast-cancer patients, we identified individuals with a germline mutation, somatic mutation, homozygous deletion, and/or hypermethylation event in BRCA1, BRCA2, and 59 other cancer-predisposition genes. Based on the assumption that BRCAness events would have similar downstream effects on tumor biology as BRCA1/BRCA2 germline mutations, we quantified these effects based on somatic-mutation signatures and gene-expression profiles. We reduced the dimensionality of the somatic-mutation signatures and expression data and used a statistical resampling approach to quantify similarities between patients who had a BRCA1/BRCA2 germline mutation, another type of aberration in BRCA1 or BRCA2, or any type of aberration in one of the other genes.ResultsSomatic-mutation signatures of tumors having a somatic mutation, homozygous deletion, or hypermethylation event in BRCA1/BRCA2 (n = 80) were generally similar to each other and to tumors from BRCA1/BRCA2 germline carriers (n = 44). Additionally, somatic-mutation signatures of tumors with germline or somatic events in ATR (n = 16) and BARD1 (n = 8) showed high similarity to tumors from BRCA1/BRCA2 carriers. Other genes also showed high similarity but only for a small number of events or for a single event type. Tumors with germline mutations or hypermethylation of BRCA1 had relatively similar gene-expression profiles and overlapped considerably with the Basal-like subtype; but the transcriptional effects of the other events lacked consistency.ConclusionsOur findings confirm previously known relationships between molecular signatures and germline or somatic events in BRCA1/BRCA2 and suggest additional genes that may be considered for inclusion in the definition of BRCAness.

scholarly journals Case Report: Effectiveness of Targeted Treatment in a Patient With Pancreatic Cancer Harboring PALB2 Germline Mutation and KRAS Somatic Mutation

2022 ◽  
Vol 8 ◽  
Author(s):  
Wei Wu ◽  
Yu Liu ◽  
Yuzhi Jin ◽  
Lulu Liu ◽  
Yixuan Guo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Next Generation Sequencing ◽  
Somatic Mutation ◽  
Germline Mutation ◽  
Tissue Sample ◽  
Rapid Development ◽  
Parp Inhibitor ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Pancreatic cancer is one of the most leading causes of cancer death worldwide. The rapid development of next-generation sequencing (NGS) and precision medicine promote us to seek potential targets for the treatment of pancreatic cancer. Here, we report a female pancreatic cancer patient who underwent radical surgical excision after neoadjuvant chemotherapy. After the surgery, the patient underwent gemcitabine + S-1 therapy, capecitabine + albumin paclitaxel therapy and irinotecan therapy successively, however, MRI review revealed tumor progression. The surgical tissue sample was subjected to next-generation sequencing (NGS), and PALB2 germline mutation and KRAS somatic mutation were identified. The patient then received olaparib (a PARP inhibitor) + irinotecan and the disease stabilized for one year. Due to the increased CA19-9, treatment of the patient with a combination of trametinib (a MEK inhibitor) and hydroxychloroquine resulted in stable disease (SD) with a significant decrease of CA19-9. This case demonstrated that the NGS may be a reliable method for finding potential therapeutic targets for pancreatic cancer.

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