Targeted molecular profiling reveals genetic heterogeneity of poromas and porocarcinomas

Bosić, Martina; Kirchner, Martina; Brašanac, Dimitrije; Leichsenring, Jonas; Lier, Amelie; Volckmar, Anna‐Lena; Oliveira, Cristiano; Buchhalter, Ivo; Stögbauer, Fabian; Živković-Perišić, Snežana; Goeppert, Benjamin; Schirmacher, Peter; Penzel, Roland; Endris, Volker

doi:10.1016/j.pathol.2017.10.011

Cited by 33 publications

(48 citation statements)

References 31 publications

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“…The altered genes were heterogeneous with only KRAS , SETD2 , and TP53 recurrently mutated in porocarcinomas. Porocarcinomas are known to be related to UV exposure and this result fits with the older median patient age (67 for poromas and 75 for carcinomas) observed in this study and suggests a more typical oncogenic mechanism involving the stochastic accumulation of mutations over time.…”

Section: Other Nutm1‐associated Solid Tumorssupporting

confidence: 88%

Emerging entities in NUTM1‐rearranged neoplasms

McEvoy

Fox

Prall

2020

Genes Chromosomes & Cancer

106

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Structural alterations of NUTM1 were originally thought to be restricted to poorly differentiated carcinomas with variable squamous differentiation originating in the midline organs of children and adolescents. Termed NUT carcinomas (NCs), they were defined by a t(15;19) chromosomal rearrangement that was found to result in a BRD4‐NUTM1 gene fusion. However, the use of DNA and RNA‐based next‐generation sequencing has recently revealed a multitude of new NUTM1 fusion partners in a diverse array of neoplasms including sarcoma‐like tumors, poromas, and acute lymphoblastic leukemias (ALLs) that we propose to call NUTM1‐rearranged neoplasms (NRNs). Intriguingly, the nosology of NRNs often correlates with the functional classification of the fusion partner, suggesting different oncogenic mechanisms within each NRN division. Indeed, whereas NCs are characterized by their aggressiveness and intransigence to standard therapeutic measures, the more positive clinical outcomes seen in some sarcoma and ALL NRNs may reflect these mechanistic differences. Here we provide a broad overview of the molecular, nosological, and clinical features in these newly discovered neoplastic entities. We describe how aberrant expression of NUTM1 due to fusion with an N‐terminal DNA/chromatin‐binding protein can generate a potentially powerful chromatin modifier that can give rise to oncogenic transformation in numerous cellular contexts. We also conclude that classification, clinical behavior, and therapeutic options may be best defined by the NUTM1 fusion partner rather than by tumor morphology or immunohistochemical profile.

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Section: Other Nutm1‐associated Solid Tumorssupporting

confidence: 88%

Emerging entities in NUTM1‐rearranged neoplasms

McEvoy

Fox

Prall

2020

Genes Chromosomes & Cancer

106

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“…EWSR1 rearrangements have been reported in single cases of porocarcinoma; however, we did not identify evidence of this rearrangement in our cohort [unpublished data]. Mutations affecting RB1 and TP53 are frequently present in porocarcinomas, and appear to be absent in poromas, suggesting a role for these tumor suppressors in malignant progression of poroid neoplasms. Additional tumor suppressors reported to be mutated in subsets of porocarcinoma include CDKN2A , APC, and PTEN …”

Section: Discussioncontrasting

confidence: 66%

“…Thus far, there is limited data regarding genetic changes associated with malignant progression in these tumors. Activating mutations in HRAS , PIK3CA , and possibly EGFR may serve as oncogenic drivers . Of these, HRAS mutations have also been reported in poromas .…”

Section: Discussionmentioning

confidence: 99%

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Altered Rb, p16, and p53 expression is specific for porocarcinoma relative to poroma

et al. 2019

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Background Porocarcinomas are rare aggressive carcinomas that harbor tumor suppressor mutations and must be distinguished from benign entities such as poromas. Methods To determine whether altered expression of these genes was diagnostically informative, we examined p53, Rb, and p16 staining patterns in 15 poromas and 16 porocarcinomas. Results Poromas consistently displayed diffuse strong expression of Rb in all but one case that displayed focal loss (1/15, 7%), and no evidence of aberrancy in p53 or p16. Porocarcinomas displayed diffuse or focal loss of Rb expression in 9/16 (56%) cases, diffuse loss or overexpression of p53 in 8/15 (53%), and diffuse loss or overexpression of p16 in 6/14 (43%). Diffuse aberrancy in p53 and Rb expression correlated with tumor mutations in TP53 and RB1, respectively, whereas focal Rb loss was associated with wild type RB1. Diffuse p16 overexpression correlated with Rb loss rather than CDKN2A mutation. For porocarcinomas with all three stains evaluable, 10/13 (77%) displayed aberrancy in at least one marker. Conclusions Our findings suggest that altered p53, p16, and/or Rb expression is relatively specific to porocarcinoma in comparison with poroma. Technical limitations of this panel, including possible focal Rb loss, must be kept in mind, especially in limited samples.

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“…The commonalities between eccrine poromas and ESFAs extend to additional shared features, including benign prognosis, rare incidence of malignant transformation, and indolent biologic behavior that obviates the need for aggressive treatment modalities . Efforts to delineate the genetic landscape of eccrine poromas and porocarcinomas are underway, and a more unified, precise nomenclature of eccrine neoplasms will facilitate future studies that rely upon an accurate categorization.…”

Section: Discussionmentioning

confidence: 99%

Reactive epidermal eccrine proliferation on the foot due to lymphedema: Eccrine poroma or syringofibroadenoma?

Hafeez

2019

J Cutan Pathol

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Targeted molecular profiling reveals genetic heterogeneity of poromas and porocarcinomas

Cited by 33 publications

References 31 publications

Emerging entities in NUTM1‐rearranged neoplasms

Emerging entities in NUTM1‐rearranged neoplasms

Altered Rb, p16, and p53 expression is specific for porocarcinoma relative to poroma

Reactive epidermal eccrine proliferation on the foot due to lymphedema: Eccrine poroma or syringofibroadenoma?

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