Dynamic, but Not Necessarily Disordered, Human-Virus Interactions Mediated through SLiMs in Viral Proteins.

Most viruses have small genomes that encode proteins needed to perform essential enzymatic functions. Across virus families, primary enzyme functions are under functional constraint; however, secondary functions mediated by exposed protein surfaces that promote interactions with the host proteins may be less constrained. Viruses often form transient interactions with host proteins through conformationally flexible interfaces. Exposed flexible amino acid residues are known to evolve rapidly suggesting that secondary functions may generate diverse interaction potentials between viruses within the same viral family. One mechanism of interaction is viral mimicry through short linear motifs (SLiMs) that act as functional signatures in host proteins. Viral SLiMs display specific patterns of adjacent amino acids that resemble their host SLiMs and may occur by chance numerous times in viral proteins due to mutational and selective processes. Through mimicry of SLiMs in the host cell proteome, viruses can interfere with the protein interaction network of the host and utilize the host-cell machinery to their benefit. The overlap between rapidly evolving protein regions and the location of functionally critical SLiMs suggest that these motifs and their functional potential may be rapidly rewired causing variation in pathogenicity, infectivity, and virulence of related viruses. The following review provides an overview of known viral SLiMs with select examples of their role in the life cycle of a virus, and a discussion of the structural properties of experimentally validated SLiMs highlighting that a large portion of known viral SLiMs are devoid of predicted intrinsic disorder based on the viral SLiMs from the ELM database.

Case-Control Study of Tumor Stage-Dependent Outcomes for Cutaneous Squamous Cell Carcinoma in Immunosuppressed and Immunocompetent Patients.

BACKGROUND: Immunosuppressed patients have worse outcomes from cutaneous squamous cell carcinomas (cSCCs), although unclear whether it is due to the development of more high-stage tumors or worse outcomes for a given stage. OBJECTIVE: Analyze the impact of immunosuppression on the development of cSCCs and tumor stage-dependent outcomes. MATERIALS AND METHODS: Single-institution 1:2 case-control study of primary invasive cSCCs from 2005 to 2015 in 106 mixed-cause immunosuppressed patients and 212 control subjects matched to age, gender, and race. RESULTS: Four hundred twelve cSCCs from 106 immunosuppressed patients and 291 tumors from 212 matched immunocompetent patients were included. Both cohorts had similar T-stage distribution, with <5% high-stage tumors, that is, AJCC-7 T2, AJCC-8 T3, and BWH T2b/T3. Immunosuppression significantly increased the likelihood of poor outcomes (POs) (aggregate of local recurrence (LR), nodal and distant metastasis, and squamous cell carcinoma-related deaths) for low-stage tumors, that is, AJCC-7 T1 (odds ratio [OR], 4.29), AJCC-8 T1 (OR, 3.45), AJCC-8 T2 (OR, 3.75), BWH T1 (OR, 3.53), and BWH T2a (OR, 3.41) tumors. There was no significant difference in the treatment: most tumors were treated with Mohs (71% vs 75%) or excision (21% vs 20%) in both cohorts. CONCLUSION: Immunosuppressed patients have an increased risk of POs, specifically LRs, from low-stage cSCCs. Definitive treatment of cSCCs is recommended.

Comparison of the American Joint Committee on Cancer Seventh Edition and Brigham and Women's Hospital Cutaneous Squamous Cell Carcinoma Tumor Staging in Immunosuppressed Patients.

BACKGROUND: The American Joint Committee on Cancer 7th edition (AJCC-7) and Brigham and Women's Hospital (BWH) staging criteria for cutaneous squamous cell carcinoma (cSCC) have not been validated in immunosuppressed patients. OBJECTIVE: To compare the AJCC-7 and BWH staging systems for cSCCs in immunosuppressed patients. MATERIALS AND METHODS: A single-institution retrospective cohort study of cSCCs in immunosuppressed patients. Risks of local recurrence (LR), nodal metastasis (NM), in-transit metastasis, and any poor outcome (PO) were compared among AJCC-7 and BWH tumor T stages. RESULTS: One hundred six patients had 412 primary invasive cSCCs. Eighty-five percent were AJCC-7 T1, and 15% T2. Risks of NM and PO for AJCC-7 T1 versus T2 were 0.9% versus 5% and 12.8% versus 23.3%, respectively, p < .05. Eighty-one percent of tumors were BWH T1, 18% T2a, 1% T2b, and 0.2% T3. Risk of LR for BWH T1 versus T2a was 11.4% versus 20.3%, p < .01. Risk of NM increased from 0.3% for T1 to 4.1%, 25%, and 100% for T2a, T2b, and T3, p < .05. Ninety percent of PO occurred in low-stage BWH T1/T2a. CONCLUSION: Low T-stage cSCCs account for most POs. Brigham and Women's Hospital staging criteria better risk stratifies cSCCs in immunosuppressed patients for risk of NM and LR.

Linear trichilemmomas on the ankle of a 28-year-old female.

Trichilemmomas are benign cutaneous proliferations derived from the outer root sheath of the hair follicle. They most often occur on the head and neck region and show a female predominance. When multiple, they are associated with Cowden syndrome (CS), a rare disorder due to an autosomal dominant germline mutation in PTEN (phosphatase and tensin homolog on chromosome 10), a tumor suppressor gene. Trichilemmomas outside of the head and neck region are rare, and as such, the association with CS is not clear. A 28-year-old healthy female with no significant family history of cancer presented to her dermatologist with multiple erythematous papules on the left anterior ankle, starting at birth. A shave biopsy confirmed the diagnosis of trichilemmoma with focal desmoplastic features (or desmoplastic trichilemmoma). A PTEN immunohistochemical study showed patchy (but not complete) loss of staining of the lesional cells. After shave removal, the trichilemmomas recurred 1-2 months later.