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Tumor Discovery Expert consensus of NUT carcinoma

neck regions. As next-generation sequencing technologies nucleosome assembly protein 1 like 4 (NAP1L4)::NUTM1
have expanded, more NUTM1 fusion partners have fusion transcript. 2,29
been identified. Consequently, NUT carcinoma is now The distinction between NUT carcinoma and other
recognized as a subtype of NUTM1-rearranged neoplasms non-NUT carcinoma is not entirely clear and is mainly
(NRNs), which also include skin tumors, sarcomas, CNS based on fusion partners, tumor origin, and pathology. The
tumors, and hematologic malignancies. 29 oncogenic mechanisms of NUT carcinoma and other non-
Skin tumors associated with NUTM1 rearrangements NUT carcinoma may differ. 2,29,42,54 Moreover, non-NUT
include classic poroma, hidradenoma simplex, dermal duct carcinoma tends to respond more favorably to standard
tumor, poroid hidradenoma, porocarcinoma, and malignant therapies, exhibit lower malignancy and invasiveness, and
poroid hidradenoma/poroid hidradenocarcinoma. The show better overall prognoses than NUT carcinoma. 29,55
fusion transcripts in these tumors primarily include yes1
associated transcriptional regulator (YAP1)::NUTM1, 4.6. Prognosis
WW domain containing transcription regulator 1 NUT carcinoma is associated with a poor prognosis and
(WWTR1):NUTM1, and endoplasmic reticulum rapid progression, with a median survival period of 6.7 –
membrane protein complex subunit 7 (EMC7)::NUTM1. 9.5 months. Many patients lose the opportunity for surgery
Sarcomas with NUTM1 rearrangements can originate due to local progression and distant metastasis. 2,15,17,30,56,57
in soft tissues, dura mater, thoracic structures, ovaries, For NUT carcinoma patients aged 7 – 16 years, the
or the colon. The relevant fusion transcripts include median survival is 8 months (ranging from 4.5 months to
MAX dimerization protein 1 (MXD1)::NUTM1, MAX 2.4 years), with 60% of cases originating in the thoracic
interactor 1 (MXI1)::NUTM1, MAX dimerization protein region (median survival of 4.5 – 15 months) and 40% in
MGA (MGA)::NUTM1, MAX dimerization protein 4 the head, neck, or adjacent to the spine (median survival
(MXD4)::NUTM1, B-cell lymphoma 6 corepressor like 1 of 10 months – 2.4 years). In a study by Chau et al.
18
58
(BCORL1)::NUTM1, and CIC::NUTM1, among others. involving 124 patients, it was reported that the prognosis for
These sarcomas can present with fibrosarcoma, epithelioid, primary NUT carcinoma originating in the thorax is worse
and rhabdomyoblastic morphology. CNS tumors linked to compared to other locations, with a higher likelihood of
NUTM1 rearrangements include fusion transcripts such as distant metastasis, larger tumors (>6 cm) that are difficult
CIC::NUTM1, ataxin 1 (ATXN1)::NUTM1, par-3 family cell to remove completely, and a mOS of only 4.4 months,
polarity regulator beta (PARD3B)::NUTM1, and spectrin resulting in a 2-year survival rate of 5%. Patients with
beta, non-erythrocytic 4 (SPTBN4)::NUTM1. Hematologic thoracic NUT carcinoma carrying the BRD4::NUTM1
malignancies associated with NUTM1 rearrangements can fusion gene have the worst prognosis. 18,59 In contrast,
occur in B-cell acute lymphoblastic leukemia (B-ALL), those without this fusion (such as BRD3::NUTM1 and
T-cell acute lymphoblastic leukemia (T-ALL), and acute NSD3::NUTM1) exhibit the best prognosis among non-
myeloid leukemia (AML). The fusion transcripts in B-ALL thoracic NUT carcinoma patients, with a 2-year survival
typically include apoptotic chromatin condensation rate of 64% and a mOS of 36.5 months. The mOS for non-
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inducer 1 (ACIN1)::NUTM1, cut-like homeobox 1 thoracic NUT carcinoma tumors with the BRD4::NUTM1
(CUX1)::NUTM1, ZNF618::NUTM1, solute carrier family fusion is 10 months. Patients with head and neck NUT
29
12 member 6 (SLC12A6)::NUTM1, chromodomain carcinoma tend to have a better prognosis compared
helicase DNA binding protein 4 (CHD4)::NUTM1, to those with tumors in the lungs and other locations
bromodomain containing 9 (BRD9)::NUTM1, AF4/FMR2 (OS: 16 months vs. 6 months). 31
family member 1 (AFF1)::NUTM1, ATPase family AAA
domain containing 5 (ATAD5)::NUTM1, Runt-related 4.7. Diagnosis
transcription factor 1 (RUNX1)::NUTM1, Ikaros family Diagnosing NUT carcinoma is challenging due to its
zinc finger 1 (IKZF1)::NUTM1, nucleosome assembly nonspecific clinical manifestations and histopathological
protein 1 like 4 (NAP1L4)::NUTM1, and apoptosis and features, which require differentiation from other small
caspase activation inhibitor (AVEN)::NUTM1. Meanwhile, round cell tumors such as Ewing sarcoma, primitive
T-ALL shows fusion transcripts such as bromodomain neuroectodermal tumor (PNET), rhabdomyosarcoma,
PHD finger transcription factor (BPTF)::NUTM1, and synovial sarcoma, undifferentiated carcinoma (including
AML demonstrates fusion transcripts such as zinc finger nasopharyngeal or salivary gland undifferentiated
and BTB domain containing 7A (ZBTB7A)::NUTM1, carcinoma), proliferative fasciitis-like low-grade
adenylate cyclase 7 (ADCY7)::NUTM1, and apoptosis and fibromyxoid sarcoma, and other poorly differentiated
caspase activation inhibitor (AVEN)::NUTM1. Myeloid or undifferentiated tumors. Similar to hematologic
1
neoplasms associated with NUTM1 mainly involve the malignancies, NUT carcinoma can also present with

Volume 3 Issue 4 (2024) 15 doi: 10.36922/td.4904