Genomic Characterization of a Rare, de Novo Unbalanced ins(3;1)(p25.3;q21.3q23.3) in a Female Child with Multiple Congenital Anomalies.

"Simple" 1-way interchromosomal insertions involving an interstitial 1q segment are rare, and therefore, their characterization at the base pair level remains understudied. Here, we describe the genomic characterization of a previously unreported de novo interchromosomal insertion (3;1) entailing an about 12-Mb pure gain of 1q21.3q23.3 that causes typical (microcephaly, developmental delay, and facial dysmorphism) and atypical (interauricular communication, small feet with bilateral deep plantar creases, syndactyly of II-IV toes, and mild pachyonychia of all toes) clinical manifestations associated with this region. Based on our analyses, we hypothesize that the duplication of a subset of morbid genes (including LMNA, USF1, VANGL2, LOR, and POGZ) could account for most clinical findings in our patient. Furthermore, the apparent disruption of a promoter region (between CPNE9 and BRPF1) and a topologically associated domain also suggests likely pathogenic reconfiguration/position effects to contribute to the patient's phenotype. In addition to further expanding the clinical spectrum of proximal 1q duplications and evidencing the phenotypical heterogeneity among similar carriers, our genomic findings and observations suggest that randomness - rather than lethality issues - may account for the paucity of "simple" interchromosomal insertions involving the 1q21.3q23.3 region as genomic donor and distal 3p25.3 as receptor. Moreover, the microhomology sequence found at the insertion breakpoint is consistent with a simple nonhomologous end-joining mechanism, in contrast to a chromothripsis-like event, which has previously been seen in other nonrecurrent insertions. Taken together, the data gathered in this study allowed us to inform this family about the low recurrence risk but not to predict the reproductive prognosis for hypothetical carriers. We highlight that genomic-level assessment is a powerful tool that allows the visualization of the full landscape of sporadic chromosomal injuries and can be used to improve genetic counseling.

Melanoma subtypes: genomic profiles, prognostic molecular markers and therapeutic possibilities.

Melanoma is characterised by its ability to metastasise at early stages of tumour development. Current clinico-pathologic staging based on the American Joint Committee on Cancer criteria is used to guide surveillance and management in early-stage disease, but its ability to predict clinical outcome has limitations. Herein we review the genomics of melanoma subtypes including cutaneous, acral, uveal and mucosal, with a focus on the prognostic and predictive significance of key molecular aberrations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.