The Expansion of the PRAME Gene Family in Eutheria

The PRAME gene family belongs to the group of cancer/testis genes whose expression is restricted primarily to the testis and a variety of cancers. The expansion of this gene family as a result of gene duplication has been observed in primates and rodents. We analyzed the PRAME gene family in Eutheria and discovered a novel Y-linked PRAME gene family in bovine, PRAMEY, which underwent amplification after a lineage-specific, autosome-to-Y transposition. Phylogenetic analyses revealed two major evolutionary clades. Clade I containing the amplified PRAMEYs and the unamplified autosomal homologs in cattle and other eutherians is under stronger functional constraints; whereas, Clade II containing the amplified autosomal PRAMEs is under positive selection. Deep-sequencing analysis indicated that eight of the identified 16 PRAMEY loci are active transcriptionally. Compared to the bovine autosomal PRAME that is expressed predominantly in testis, the PRAMEY gene family is expressed exclusively in testis and is up-regulated during testicular maturation. Furthermore, the sense RNA of PRAMEY is expressed specifically whereas the antisense RNA is expressed predominantly in spermatids. This study revealed that the expansion of the PRAME family occurred in both autosomes and sex chromosomes in a lineage-dependent manner. Differential selection forces have shaped the evolution and function of the PRAME family. The positive selection observed on the autosomal PRAMEs (Clade II) may result in their functional diversification in immunity and reproduction. Conversely, selective constraints have operated on the expanded PRAMEYs to preserve their essential function in spermatogenesis

Exploratory analysis of immunochemotherapy compared to chemotherapy after EGFR‐TKI in non–small cell lung cancer patients with EGFR mutation: A multicenter retrospective study

Abstract Background Patients with epidermal growth factor receptor (EGFR)‐mutated, advanced non–small cell lung cancer have received immunochemotherapy as one of the treatment options after tyrosine kinase inhibitor (TKI) failure. Methods We retrospectively examined EGFR‐mutant patients treated with atezolizumab‐bevacizumab‐carboplatin‐paclitaxel (ABCP) therapy or platinum‐based chemotherapy (Chemo) after EGFR‐TKI therapy at five institutions in Japan. Results A total of 57 patients with EGFR mutation were analyzed. The median progression‐free survival (PFS) and overall survival (OS) in the ABCP (n = 20) and Chemo (n = 37) were 5.6 and 20.9 months, 5.4 and 22.1 months, respectively (PFS, p = 0.39; OS, p = 0.61). In programmed death‐ligand 1 (PD‐L1)–positive patients, median PFS in the ABCP group was longer than in the Chemo group (6.9 vs. 4.7 months, p = 0.89). In PD‐L1–negative patients, median PFS in the ABCP group was significantly shorter than in the Chemo group (4.6 vs. 8.7 months, p = 0.04). There was no difference in median PFS between the ABCP and Chemo groups in the subgroups of brain metastases, EGFR mutation status, or chemotherapy regimens, respectively. Conclusion The effect of ABCP therapy and chemotherapy was comparable in EGFR‐mutant patients in a real‐world setting. The indication for immunochemotherapy should be carefully considered, especially in PD‐L1–negative patients

Comparison of the efficiencies of different affinity tags in the purification of a recombinant secretory protein expressed in silkworm larval hemolymph

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Liquid biopsy detects genomic drivers in NSCLC without EGFR mutations by single‐plex testing: WJOG13620L

Abstract Background Actionable tumor genomic alterations, primarily EGFR mutations, occur in nearly 70% of Japanese advanced nonsquamous non‐small cell lung cancer (NSCLC) patients. Standard assessment of tumor tissue includes rapid testing for EGFR mutations, ALK fusions and ROS1 fusions. We conducted a prospective observational study (WJOG13620L) of follow‐on next‐generation sequencing of circulating tumor DNA (ctDNA) in patients without driver alterations after EGFR testing. Methods Patients with untreated advanced (Stage IIIB–IV or relapsed) nonsquamous NSCLC without EGFR mutations according to single‐plex testing of tumor tissue, were enrolled into this study. Patients with other known driver mutations or who underwent comprehensive genomic profiling were excluded. Plasma was analyzed by Guardant360, and the primary endpoint was the proportion of patients with pathogenic gene alterations in at least one of nine genes. Results Among the 72 patients enrolled, ALK and ROS1 fusions were tested in 86.1% and 65.2%, respectively. Alterations in pre‐defined genes were detected in 21 patients (29.2%; 95% confidence interval: 19.0–41.1, p < 0.001 [one‐sided null hypothesis proportion of 10%]), including RET fusion (n = 1) and mutations in KRAS (n = 11), EGFR (n = 5), ERBB2 (n = 3), and BRAF (n = 1). Median time from sample submission to results was 8 days (range, 5–17 days). Conclusion Rapid follow‐on comprehensive testing of ctDNA should be considered prior to first‐line treatment for patients with advanced nonsquamous NSCLC when no alterations are detected after single‐plex tissue testing