Effectiveness of alectinib and osimertinib in a brain metastasized lung adenocarcinoma patient with concurrent EGFR mutations and DCTN1-ALK fusion

The echinoderm microtubule associated protein-like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non-small-cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)-ALK rearrangement is extremely rare. The co-occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1-ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions ..... READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.14291

Authors: Shuyuan Wang, Bo Yan, Yanwei Zhang, Jianlin Xu, Rong Qiao, Yu Dong, Bo Zhang, Yiming Zhao, Lele Zhang, Jie Qian, Jun Lu, Ruiying Zhao, Baohui Han

Case Study, group1Kirk SmithDecember 28, 2021alectinib, osimertinib, brain metastasis, ALK, lung, EGFR, DCTN1-ALK

Significance of TP53 Mutation in Cellular Process and Disease Progression in Lung Adenocarcinoma

Analysis of the TCGA data showed TP53 mutations in 22% of LUAD patients. Clinicopathological analyses demonstrated that TP53 mutation was correlated with the disease progression but not prognosis. We identified 1935 differentially expressed genes (DEGs). Functional enrichment analysis showed that the DEGs were mainly concentrated in metabolism, cell differentiation, and cancer-related pathways. The top hub genes were identified and disease analysis revealed the most critical genes related to disease progression and prognosis. The expression levels of several of these genes were then tested in tumor tissues. Our results showed that TP53 mutation plays a critical role in cellular process and the clinicopathological findings in LUAD. We also identified potential key genes, which could provide novel evidence for individualized treatment. READ ARTICLE

Genetic Testing and Molecular Biomarkers DOI:10.1089/gtmb.2020.0304

Authors: Yongbo Hou, Sheng Tan, Guoxiang Wang

Real-World OutcomesKirk SmithMay 1, 2021TP53, adenocarcinoma, lung

Prevalence and potential biological role ofTERTamplifications inALKtranslocated adenocarcinoma of the lung

The advent of specific ALK-targeting drugshas radically changed the outcome of patients withALKtranslocated non-small-cell lung cancer(NSCLC). However, emerging resistance to treatmentwithALKinhibitors in these patients remains amajor concern. In previous studies, we analysed twoALK+patient cohorts (TP53wild-type/TP53mutated) in terms of copy number alterations. Allpatients belonging to theTP53wild-type group hadmainly genetically stable genomes, with one excep-tion showing chromosomal instability and amplifica-tions of several gene loci, includingTERT. Here, weaimed to determine the prevalence ofTERTamplifi-cations in theseALK+lung cancer patients by ana-lysing an independent cohort of 109ALKtranslocated cases. We further analysed the copy numbers of numerous cancer-relevant genes andother genetic aberrations. The prevalence ofTERTamplifi-cations was determined by means of FISH analyses.Copy numbers of 87 cancer-relevant genes were deter-mined by NanoString nCounterâtechnolo..... READ ARTICLE

Histopathology DOI:10.1111/his.14256

Authors: Alidousty C, Duerbaum N, Wagener-Ryczek S, Baar T, Martelotto L G, Heydt C, Siemanowski J, Holz B, Binot E,Fassunke J, Merkelbach-Bruse S, Wolf J, Kron A, Buettner R, Schultheis A M