The neural crest origin of uveal melanomas

Abstract

On the basis of two cases the relation between 'neurogenic' tumours (neurinomas, neurilemmomas, Schwannomas, neurofibromas) and malignant melanomas of the uvea is discussed with emphasis on the close association of both groups of neoplasms with the ciliary nerves. The great histopathological diversity between different cases of melanoma as well as within individual cases is also pointed out. On histological and cytological criteria it may be difficult to differentiate between the 'neurogenic' tumours and the highly differentiated, spindle cell variants of the melanomas. Since all these tumours are derived from the neural crest, they might be grouped under one common heading. It is postulated that 'neurogenic' tumours have been overdiagnosed to the disadvantage of the highly differentiated spindle cell melanomas.

GNAQ Induces Melanomagenesis in Mitfa-Independent Melanocyte Progenitors in a Zebrafish Model of Uveal Melanoma

“…(B) Schematic of TEAZ-Skin using wild type ( AB ), nacre ( mitfa w 2 /w 2 ) and casper ( mitfa w 2 /w 2 : mpv17 a 9 /a 9 ) zebrafish lines.…”

“…We applied TEAZ to the skin (TEAZ-Skin) of adult wild-type ( AB ), mitfa w 2 /w 2 ( nacre 43 ), and mitfa w 2 /w 2 ; mpv17 a 9 /a 9 ( casper 46,47 ) zebrafish to validate the oncogenic potential of GNAQ Q209L ( Figure 1B ). TEAZ-Skin using Strategy A and Strategy B induced melanoma in wild-type zebrafish within an average of 147- and 104-days, respectively ( Figure 1C-D, Figure S1A ).…”

“…(n=5 for Strategy B, n=3 for rest) ( B’ ) Representative brightfield and fluorescent images shown at 2, 4, and 6 weeks for strategy B injection in nacre . ( C ) Kaplan-Meier curves estimating tumor-free survival in adult casper ( mitfa w2/w2 , mpv17 a9/a9 ) zebrafish via TEAZ-Skin. Same injection mixes as in (A).…”

GNAQ Induces Melanomagenesis in Mitfa-Independent Melanocyte Progenitors in a Zebrafish Model of Uveal Melanoma

“…(B) Schematic of TEAZ-Skin using wild type ( AB ), nacre ( mitfa w 2 /w 2 ) and casper ( mitfa w 2 /w 2 : mpv17 a 9 /a 9 ) zebrafish lines.…”

“…We applied TEAZ to the skin (TEAZ-Skin) of adult wild-type ( AB ), mitfa w 2 /w 2 ( nacre 43 ), and mitfa w 2 /w 2 ; mpv17 a 9 /a 9 ( casper 46,47 ) zebrafish to validate the oncogenic potential of GNAQ Q209L ( Figure 1B ). TEAZ-Skin using Strategy A and Strategy B induced melanoma in wild-type zebrafish within an average of 147- and 104-days, respectively ( Figure 1C-D, Figure S1A ).…”

“…(n=5 for Strategy B, n=3 for rest) ( B’ ) Representative brightfield and fluorescent images shown at 2, 4, and 6 weeks for strategy B injection in nacre . ( C ) Kaplan-Meier curves estimating tumor-free survival in adult casper ( mitfa w2/w2 , mpv17 a9/a9 ) zebrafish via TEAZ-Skin. Same injection mixes as in (A).…”

PHA665752 inhibits the HGF-stimulated migration and invasion of cells by blocking PI3K/AKT pathway in uveal melanoma

“…Uveal melanoma (UM) is the most common primary malignance in adults [1] and originates from uveal melanocytes, including those of the choroid, ciliarybody, and iris [2]. Despite the existence of a number of effective therapeutic options to eradicate primary UMs and to prevent their local recurrence [3], there are currently no systematic curative therapies for metastatic UMs [4,5].…”

YAP inhibition blocks uveal melanogenesis driven by GNAQ or GNA11 mutations

“……”

GNAQ Induces Melanomagenesis in Mitfa-Independent Melanocyte Progenitors in a Zebrafish Model of Uveal Melanoma

“…(B) Schematic of TEAZ-Skin using wild type ( AB ), nacre ( mitfa w 2 /w 2 ) and casper ( mitfa w 2 /w 2 : mpv17 a 9 /a 9 ) zebrafish lines.…”

“…We applied TEAZ to the skin (TEAZ-Skin) of adult wild-type ( AB ), mitfa w 2 /w 2 ( nacre 43 ), and mitfa w 2 /w 2 ; mpv17 a 9 /a 9 ( casper 46,47 ) zebrafish to validate the oncogenic potential of GNAQ Q209L ( Figure 1B ). TEAZ-Skin using Strategy A and Strategy B induced melanoma in wild-type zebrafish within an average of 147- and 104-days, respectively ( Figure 1C-D, Figure S1A ).…”

“…(n=5 for Strategy B, n=3 for rest) ( B’ ) Representative brightfield and fluorescent images shown at 2, 4, and 6 weeks for strategy B injection in nacre . ( C ) Kaplan-Meier curves estimating tumor-free survival in adult casper ( mitfa w2/w2 , mpv17 a9/a9 ) zebrafish via TEAZ-Skin. Same injection mixes as in (A).…”

PHA665752 inhibits the HGF-stimulated migration and invasion of cells by blocking PI3K/AKT pathway in uveal melanoma

“…Uveal melanoma (UM) is the most common primary malignance in adults [1] and originates from uveal melanocytes, including those of the choroid, ciliarybody, and iris [2]. Despite the existence of a number of effective therapeutic options to eradicate primary UMs and to prevent their local recurrence [3], there are currently no systematic curative therapies for metastatic UMs [4,5].…”

YAP inhibition blocks uveal melanogenesis driven by GNAQ or GNA11 mutations

“……”

GNAQ Induces Melanomagenesis in Mitfa-Independent Melanocyte Progenitors in a Zebrafish Model of Uveal Melanoma

“…(B) Schematic of TEAZ-Skin using wild type ( AB ), nacre ( mitfa w 2 /w 2 ) and casper ( mitfa w 2 /w 2 : mpv17 a 9 /a 9 ) zebrafish lines.…”

“…We applied TEAZ to the skin (TEAZ-Skin) of adult wild-type ( AB ), mitfa w 2 /w 2 ( nacre 43 ), and mitfa w 2 /w 2 ; mpv17 a 9 /a 9 ( casper 46,47 ) zebrafish to validate the oncogenic potential of GNAQ Q209L ( Figure 1B ). TEAZ-Skin using Strategy A and Strategy B induced melanoma in wild-type zebrafish within an average of 147- and 104-days, respectively ( Figure 1C-D, Figure S1A ).…”

“…(n=5 for Strategy B, n=3 for rest) ( B’ ) Representative brightfield and fluorescent images shown at 2, 4, and 6 weeks for strategy B injection in nacre . ( C ) Kaplan-Meier curves estimating tumor-free survival in adult casper ( mitfa w2/w2 , mpv17 a9/a9 ) zebrafish via TEAZ-Skin. Same injection mixes as in (A).…”

PHA665752 inhibits the HGF-stimulated migration and invasion of cells by blocking PI3K/AKT pathway in uveal melanoma

“…Uveal melanoma (UM) is the most common primary malignance in adults [1] and originates from uveal melanocytes, including those of the choroid, ciliarybody, and iris [2]. Despite the existence of a number of effective therapeutic options to eradicate primary UMs and to prevent their local recurrence [3], there are currently no systematic curative therapies for metastatic UMs [4,5].…”

YAP inhibition blocks uveal melanogenesis driven by GNAQ or GNA11 mutations

“……”