Endocrine Abstracts

Introduction: Our knowledge of the genomic background of neuroendocrine neoplasms (NENs) is rapidly expanding with more widespread use of sequencing technologies. Although known to be mutationally quiet compared to some other malignancies, many NENs harbour somatic copy number alterations (SCNAs), however the significance of these are unclear.

Aims: We sought to identify SCNAs in a cohort of patients with NENs.

Methods: Whole exome sequencing was performed on DNA extracted from formalin-fixed paraffin embedded tumour samples and matched leucocytes (as a normal germline control), for 9 patients with NENs (6 small intestinal, 1 ovarian, 1 pelvic and 1 lung). Established in-house bioinformatics pipelines were used to identify SCNAs in each tumour DNA sample.

Results: Gene and region specific amplifications and deletions were detected in all patients. Deletion of 1 copy of chromosome 18 was detected in 8 of 9 patients (89%), the exception being the patient with lung carcinoid. Loss of chromosome 9 was observed in 3 patients (2 small intestinal plus ovarian). Gains of chromosome 5 and chromosome 20 (CN=3) were observed in 3 patients each (3 small intestinal and 2 small intestinal plus ovarian respectively).

Conclusion: Loss of heterozygosity is common to NENs and in particular loss of chromosome 18 including the DCC gene was common in this small cohort of NENs. Previous molecular studies have shown reduced expression of DCC in NENs suggesting this as a candidate tumour suppressor in these cancers. Future molecular mechanistic studies on these commonly affected chromosomes may help identify other important genes that drive NEN tumourigenesis.