Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors

Abstract

Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors. We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, TC and AC, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum. Analysis of sequencing data found recurrent mutations in cancer genes including , and The mutated genes are involved in biological processes including cellular metabolism, cell division cycle, cell death, apoptosis, and immune regulation. The top most significantly mutated genes were and Pathway analysis of significantly mutated and cancer driver genes implicated MAPK/ERK and amyloid beta precursor protein (APP) pathways whereas analysis of CNV and gene expression data suggested deregulation of the NF-κB and MAPK/ERK pathways. The mutation signature was predominantly C>T and T>C transitions with a minor contribution of T>G transversions. This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors. .

Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single‑center retrospective cohort study and literature review

“…In addition, Rossi et al (40) also reported that ERBB4 alteration was detected in carcinoids. Recently, Asiedu et al (41) used mRNA expression, single nucleotide polymorphism genotyping and a combination of exome and whole-genome sequencing to detect genomic alterations in 31 TC and 11 AC tumors. Compared with the results of Asiedu et al (41), only a limited number of mutated genes were common to the genes identified using NGS in the present study.…”

“…Recently, Asiedu et al (41) used mRNA expression, single nucleotide polymorphism genotyping and a combination of exome and whole-genome sequencing to detect genomic alterations in 31 TC and 11 AC tumors. Compared with the results of Asiedu et al (41), only a limited number of mutated genes were common to the genes identified using NGS in the present study. The differences between the current study and the previous studies may be attributable to the examination of different targeted gene panels and the different demographic of patients included.…”

Molecular Classification of Neuroendocrine Tumors of the Thymus

“…NF1 mutations have also been described in pulmonary carcinoids and in pheochromocytomas, albeit at much lower frequency. 36,37 Somatic NF1 mutations occur in many sporadic cancers including lung 4cancer, melanoma, ovarian carcinoma, and pheochromocytoma. 37,38 Due to the lack of normal control tissues, we could not differentiate between NF1 somatic and germline mutations.…”

TAF1L promotes development of oral squamous cell carcinoma via decreasing autophagy-dependent apoptosis

“…Our primary studies via bioinformatics, RNA-seq and multiple immunohistochemistry revealed that TAF1L gene with somatic mutations and overexpression, as an oncogene, could promote OSCC and esophageal cancer procession [12,13]. Subsequently, growing studies have reported that deletions, point mutations, abnormal expression and inactivation of TAF1L were involved in the tumorigenesis of several cancers, such as lung, oral, gastric, colorectal, and urothelial cancers [14][15][16][17]. However, more researches for the roles of TAF1L gene in tumorigenesis are still needed.…”