Oncogenic KIT mutations in different exons lead to specific changes in melanocyte phospho-proteome

Sanlorenzo, Martina; Vujic, Igor; Posch, Christian; Ma, Jeffrey; Lin, Kai; Lai, Kevin; Lee, D.; Vujic, Marin; Oses-Prieto, Juan; Chand, Shreya; Rodríguez-Peralto, José L.; Burlingame, Alma L.; Ortiz‐Urda, Susana

doi:10.1016/j.jprot.2016.05.019

Cited by 8 publications

(8 citation statements)

References 41 publications

(40 reference statements)

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“…The proto-oncogene c-KIT encodes for the tyrosine kinase receptor (CD117) and is involved in cell signal transduction with different downstream pathways: MAPK, phosphatidylinositol 3-kinases (PI3K), Janus kinase (JAK)/signal transducers and activators of transcription (STAT), SRC family kinases (SFK) and phospholipase Cγ [ 5 ]. Furthermore, c-KIT is a mutagenic effective proto-oncogene with a stem-cell factor (SCF) as a ligand, and it leads to tumor growth through impairment of cellular growth regulation [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Loss of c-KIT expression in thyroid cancer cells

et al. 2017

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Papillary thyroid carcinoma is the most frequent histologic type of thyroid tumor. Few studies investigated the role of c-KIT expression in thyroid tumors, suggesting a role for this receptor and its ligand in differentiation and growth control of thyroid epithelium and a receptor loss following malignant transformation. We investigated and correlated c-KIT expression levels and two known markers of thyrocytes differentiation, PAX8 and TTF-1, in malignant and benign cytological thyroid samples. Moreover, we performed functional studies on human papillary thyroid carcinoma cell line to associated c-KIT expression to thyrocytes differentiation and tumor proliferation. c-KIT and PAX8 expression resulted higher in benign samples compared to the malignant ones, and the expression levels of these two genes were significantly correlated to each other. We also observed that c-KIT overexpression led to an increase of PAX8 expression level together with a decrease of proliferation. Furthermore, c-KIT overexpressing cells showed a regression of typical morphological features of malignancy. Taken together these results suggest that c-KIT could be involved in the differentiation of thyroid cells and in tumor progression.

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Section: Introductionmentioning

confidence: 99%

Loss of c-KIT expression in thyroid cancer cells

et al. 2017

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“…A small number of studies have researched the role of KIT in PTC. Sanlorenzo et al (42) mentioned that the proto-oncogene KIT encodes for the tyrosine kinase receptor and is involved in cell signal transduction with different downstream pathways: MAPK, phosphatidylinositol 3-kinases (PI3K), Janus kinase (JAK)/signal transducers and activators of transcription (STAT), SRC family kinases (SFK) and phospholipase Cg (42). On the other hand, the mitogen-activated protein kinase (MAPK) pathway has been extensively researched, and the role of point mutations in the BRAF and RAS genes and RET/PTC rearrangements in PTC molecular pathogenesis has been described (43,44).…”

Section: Discussionmentioning

confidence: 99%

Identification of KIT and BRAF mutations in thyroid tissue using next-generation sequencing in an Ecuadorian patient: A case report

et al. 2023

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BackgroundThe incidence of thyroid cancer has increased worldwide. Ecuador presents the highest incidence among Latin American countries and the second around the world. Genetic alteration is the driving force for thyroid tumorigenesis and progression. The change from valine (V) to glutamic acid (E) at codon 600 of the BRAF gene (BRAFVal600Glu) is the most commonly reported mutation in thyroid cancer. Moreover, the BRAF mutation is not the only mutation that has been correlated with TC. For instance, mutations and overexpression of the KIT gene has been associated with different types of cancer, including lung and colon cancer, and neuroblastoma.Case presentationA woman in her early fifties, self-identified as mestizo, from Otavalo, Imbabura-Ecuador had no systemic diseases and denied allergies, but she had a family history of a benign thyroid nodule. Physical examination revealed a thyroid gland enlargement. The fine-needle aspiration biopsy indicated papillary thyroid cancer. The patient underwent a successful total thyroidectomy with an excellent recovery and no additional treatments after surgery. Using Next-Generation sequencing a heterozygous mutation in the BRAF gene, causing an amino acid change Val600Glu was identified. Similarly, in the KIT gene, a heterozygous mutation resulting in an amino acid change Leu678Phe was detected. Moreover, an ancestry analysis was performed, and the results showed 3.1% African, 20.9% European, and 76% Native American ancestry.ConclusionsThis report represents the genetic characteristics of papillary thyroid cancer in an Ecuadorian woman with a mainly Native American ethnic component. Further studies of pathological variants are needed to determine if the combined demographic and molecular profiles are useful to develop targeted treatments focused on the Ecuadorian population.

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“…These mutations are shown to occur in the tyrosine kinase domain 1 (TK1, exon 17) and the juxtadomain region (JM, exon 11). Less common mutations occur in the extracellular domain (exons 2, 8, and 9), as well as tyrosine kinase domain 2 (TK2, exons 13, and 14) [ 41 ]. These mutations can occur in a variety of ways, such as point mutations, frame deletions, and internal tandem repeats, but rarely do we find more than one mutation of CD117 in tumors.…”

Section: The Cd117 Receptormentioning

confidence: 99%

CD117/c-kit in Cancer Stem Cell-Mediated Progression and Therapeutic Resistance

et al. 2018

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Metastasis is the primary cause of cancer patient morbidity and mortality, but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patient tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven by a cancer stem-like cell or tumor progenitor cell, while recurrence at a secondary site is driven by metastatic cancer stem cells or metastasis-initiating cells. Ongoing efforts are aimed at identifying and characterizing these stem-like cells driving recurrence and metastasis. One potential marker for the cancer stem-like cell subpopulation is CD117/c-kit, a tyrosine kinase receptor associated with cancer progression and normal stem cell maintenance. Further, activation of CD117 by its ligand stem cell factor (SCF; kit ligand) in the progenitor cell niche stimulates several signaling pathways driving proliferation, survival, and migration. This review examines evidence that the SCF/CD117 signaling axis may contribute to the control of cancer progression through the regulation of stemness and resistance to tyrosine kinase inhibitors.

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Oncogenic KIT mutations in different exons lead to specific changes in melanocyte phospho-proteome

Cited by 8 publications

References 41 publications

Loss of c-KIT expression in thyroid cancer cells

Loss of c-KIT expression in thyroid cancer cells

Identification of KIT and BRAF mutations in thyroid tissue using next-generation sequencing in an Ecuadorian patient: A case report

CD117/c-kit in Cancer Stem Cell-Mediated Progression and Therapeutic Resistance

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