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Neuroendocrine tumors (NETs) are a type of rare tumor that can occur at multiple organs. Rectal NETs are the most common NETs in gastrointestinal tract. Due to the rarity of rectal NETs in rectal cancer, the molecular features and the correlation with patient therapeutic response and prognosis have not been investigated in detail. In this review, we focused on the molecular features, potential therapeutic targets and prognosis of rectal NETs. By summarizing the relevant studies, we established the mutational landscape of rectal NETs and identified a series of large fragment variations. Driver genes including TP53, APC, KRAS, BRAF, RB1, CDKN2A and PTEN were found as the top mutated genes. Large fragment alterations mainly involved known driver genes, including APC, TP53, CCNE1, MYC, TERT, RB1 and ATM. Germline mutations of APC, MUTYH, MSH6, MLH1 and MSH2 associated with Lynch syndrome or FAP were also found in rectal NETs. The BRAF-V600E mutation was reported as an actionable target in rectal NETs, and the combined BRAF/MEK inhibitors were found to be effective targeting BRAF-V600E in advanced or metastatic NETs. The known prognostic risk factors of rectal adenocarcinoma, including a series of demographic and clinicopathological factors were also prognostic factors for rectal NETs. Furthermore, three types of markers, including genetic alterations, protein expression levels and methylation, were also suggested as prognostic factors for rectal NETs. In summary, we established the landscape of mutations and large-fragment alterations of rectal NETs, and identified potential therapeutic targets and a series of prognostic factors. Future studies may focus on the optimization of therapeutic strategies based on potential actionable biomarkers.

A total of 100 EDTA-blood samples were obtained from unrelated individuals of Chinese Han ethnic group in Chengdu of China. DNA was extracted by utilizing the Chelex-100 method as described by Walsh et al. (1). The allelic variation at three STR loci named as D12S2080, D16S2619 and D9S1119 were analyzed by PCR amplification whose respective conditions can be accessed at Nucleotide Database updated by NCBI (http://www.ncbi.nlm.nih.gov), however, their annealing temperatures do not totally amount to those recommended by Database. The details of PCR conditions are described in Table 1. The volume of PCR reaction for each locus was 20 µL containing 2-10 ng DNA, 1 × Taq buffer, 1.5 mM MgCl2, 200 µM each dNTP (Pharmacia Biotech, Sweden), 2.0 U Taq polymerase and 0.3 µM each primer. PCR amplifications were carried out in a GeneAmp PCR System 9600 (Perkin-Elmer).The respective primers of these three loci are described in Table 2.