<abstract xmlns="http://www.w3.org/1999/xhtml">
<sec id="j_jmotherandchild.20212501.d-21-00007_s_007">
<h3>Background</h3>
<p>Large and giant congenital melanocytic nevi (CMN), benign naevomelanocytic proliferations derived from neural crests, with a projected adult size (PAS) ≥ 20 cm, are connected to a high risk of melanoma and neurocutaneous melanosis. Among several factors, genetic alterations seem to be involved in tumorigenesis. The aim of the present study was to analyse the mutation status of <italic>NRAS</italic> and <italic>BRAF</italic> genes in resection specimens from large or giant CMN in a group of Polish patients.</p></sec>
<sec id="j_jmotherandchild.20212501.d-21-00007_s_008">
<h3>Material and methods</h3>
<p>The formalin-fixed, paraffin-embedded resection specimens from 18 patients, fixed in the years of 2006 to 2017, were included in the study. The regions containing the highest load of melanocytes were macrodissected prior to DNA isolation. The <italic>NRAS</italic> and <italic>BRAF</italic> mutation status was evaluated using qPCR.</p></sec>
<sec id="j_jmotherandchild.20212501.d-21-00007_s_009">
<h3>Results</h3>
<p>We detected activating mutations in <italic>NRAS</italic> gene (codons: 12 and 61) in 7 out of the 18 (38.9%) patients. No <italic>BRAF</italic> mutations were found.</p></sec>
<sec id="j_jmotherandchild.20212501.d-21-00007_s_010">
<h3>Conclusion</h3>
<p>Our study, the first molecular analysis of large/giant CMN in Polish patients, supports the hypothesis that <italic>NRAS</italic> mutation in codon 61 are frequent, recurrent mutations in large/giant CMN. Moreover, we show, for the first time, that <italic>NRAS</italic> mutations in codon 12 (p.Gly12Asp) can be also detected in giant CMN. The exact role of these genetic alterations in CMN formation remains to be elucidated.</p></sec>
</abstract>

Background
Large and giant congenital melanocytic nevi (CMN), benign naevomelanocytic proliferations derived from neural crests, with a projected adult size (PAS) ≥ 20 cm, are connected to a high risk of melanoma and neurocutaneous melanosis. Among several factors, genetic alterations seem to be involved in tumorigenesis. The aim of the present study was to analyse the mutation status of NRAS and BRAF genes in resection specimens from large or giant CMN in a group of Polish patients.

Material and methods
The formalin-fixed, paraffin-embedded resection specimens from 18 patients, fixed in the years of 2006 to 2017, were included in the study. The regions containing the highest load of melanocytes were macrodissected prior to DNA isolation. The NRAS and BRAF mutation status was evaluated using qPCR.

Results
We detected activating mutations in NRAS gene (codons: 12 and 61) in 7 out of the 18 (38.9%) patients. No BRAF mutations were found.

Conclusion
Our study, the first molecular analysis of large/giant CMN in Polish patients, supports the hypothesis that NRAS mutation in codon 61 are frequent, recurrent mutations in large/giant CMN. Moreover, we show, for the first time, that NRAS mutations in codon 12 (p.Gly12Asp) can be also detected in giant CMN. The exact role of these genetic alterations in CMN formation remains to be elucidated.

The retrospective molecular analysis of large or giant congenital melanocytic nevi in a group of Polish children

Journal of Mother and Child

This work is licensed under the Creative Commons Attribution 4.0 International License.

Background
Large and giant congenital melanocytic nevi (CMN), benign naevomelanocytic proliferations derived from neural crests, with a projected adult size...

Patient No	Year of birth/sex	Localization of nevus	Melanoma arising in the nevus	Neurocutaneous melanosis (NCM)	Age during first operation	Number of operations	Treatment completed	CMN size	Satellite nevi	BRAF variants detected	NRAS variants detected
1	2011/m	B			6/12	5	+	>20 cm	+	none	p.Gln61Lys
2	2012/m	H		+	7/12	4		> 0,5% PAS	0	none	none
3	2012/m	H			1/12	2	+	0,5 % PAS	0	none	p.Gln61Lys
4	2009/f	BT			4y	6		> 20 cm	++	none	none
5	1989/f	N			15y	4	+	> 20 cm	0	none	none
6	2003/f	B			1/12	5	+	> 20 cm	+	none	none
7	2007/f	BT		+	1/12	14		> 20 cm	0	none	none
8	2011/m	B			3/12	2	+	> 20 cm	0	none	p.Gln61Lys
9	2009/f	B			4/12	8	+	> 20 cm	+	none	none
10	2007/f	H			2y	8		> 0,5% PAS	+	none	p.Gln61Lys
11	2011/f	B			3/12	5	+	> 20 cm	+	none	p.Gly12Asp
12	2006/m	BT		+	4/12	21		> 20 cm	nd	none	none
13	2009/m	B		+	2y	5		> 20 cm	++	none	p.Gln61Lys
14	2002/m	BT			2y	10	+	not assessed	0	none	p.Gln61Arg
15	2012/m	HN			3/12	2		> 0,5% PAS	0	none	none
16	2010/f	B		+	6/12	4	+	> 20 cm	+	none	none
17	2006/f	BT	+	+	6/12	13	+	> 20 cm	nd	none	none
18	2008/m	H	+	+	1/12	3	+	> 0,5% PAS	-	none	none

The retrospective molecular analysis of large or giant congenital melanocytic nevi in a group of Polish children

Article Category: Original paper

Pubblicato online: 11 ott 2021

Pagine: 19 - 24

Ricevuto: 07 mar 2021

Accettato: 22 apr 2021

DOI: https://doi.org/10.34763/jmotherandchild.20212501.d-21-00007

Parole chiave
Congenital melanocytic nevi, CMN, GCMN, NRAS

© 2021 Katarzyna Wertheim-Tysarowska et al. published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Characteristics of patients and results of molecular investigation

The retrospective molecular analysis of large or giant congenital melanocytic nevi in a group of Polish children

Article Category: Original paper

Pubblicato online: 11 ott 2021

Pagine: 19 - 24

Ricevuto: 07 mar 2021

Accettato: 22 apr 2021

DOI: https://doi.org/10.34763/jmotherandchild.20212501.d-21-00007

Parole chiaveCongenital melanocytic nevi, CMN, GCMN, NRAS

© 2021 Katarzyna Wertheim-Tysarowska et al. published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Characteristics of patients and results of molecular investigation

Parole chiave
Congenital melanocytic nevi, CMN, GCMN, NRAS