Increased risk of internal tumors in DNA repair-deficient xeroderma pigmentosum patients: analysis of four international cohorts

Nikolaev, Sergey; Yurchenko, Andrey A.; Sarasin, Alain

doi:10.1186/s13023-022-02203-1

Orphanet Journal of Rare Diseases

Table 3 All reported xeroderma pigmentosum patients with internal tumor*

From: Increased risk of internal tumors in DNA repair-deficient xeroderma pigmentosum patients: analysis of four international cohorts

Source (years of follow-up, city, country)	No. of XP patients with internal tumor/no. of reported XP patients in the publications	Countries of origin of described XP patients	Genotype of XP patients with internal tumors	Type of internal tumor^† (age at diagnosis, sex, country, cell code)	Additional clinical information
Berlin and Tager, (1953–1958, Tel Aviv) and Yosipovitch et al. (1955–1963, Jerusalem, Israel) [19, 20]	1/25	4 countries of Middle East	Med Basin^‡	Myeloid leukemia (32y, M, Iraq)	Death at 35y
Reed et al.,1969 (Los Angeles, United States) [21]	1/5	United Kingdom	XP-A or XP-D^$	Acute lymphatic leukemia (3y,M)	Death at 6y
Kraemer et al.,1984 and Kraemer et al.,1987 (1874–1982, Bethesda, United States) [10, 17]	14/830	41 different countries	NR^\|\|	Astrocytoma (9y, M, Japan)
			NR	Medulloblastoma (14y, M, NIH^¶)
			NR	Brain sarcoma (16y, M, NIH)
			NR	Brain sarcoma (33y, M, NIH)	Death at 35y
			XPC: c.621_622ins83	Bronchogenic carcinoma (34y, M, NIH, XP3BE)	Death at 37y
			NR	Bronchogenic carcinoma (62y, M, France)
			NR	Pancreatic adenocarcinoma (47y, F, Spain)
			NR	Breast cancer (38y, F, NIH)
			NR	Throat cancer (65y, M, NIH)
			NR	Gastric cancer (67y, M, France)
			NR	Testicular cancer (12y, M, NIH)
			NR	Gingival squamous cell (9y, F, NIH)
			NR	Gingival tumor (17y, F, NIH)
			NR	Palate squamous cell (18y, M, NIH)
Puig et al.,1985 (Spain) [22]	1/1	Spain	NR	Gastric adenocarcinoma (30y, F)	Death at 31y
Satoh and Nishigori, 1988 (1975–1987, Kyoto, Japan) [23]	6/272	Japan	XP-A	Glioblastoma (8y, F)	Death at 9y
			XP-F	Bile duct carcinoma (60y, F)	Death at 65y
			XP-V	Transitional cell carcinoma of bladder (68y, M)	Death at 68y
			XP-V	Stomach carcinoma (53y, M)	Death at 53y
			XP-V	SCC of pharynx (51y, M)	Death at 56y
			NR	Uterine carcinoma (49y, F)	Death at 51y
Berbis et al.,1989 (Bordeaux, France) [24]	2/2	Algeria	XPC: delTG^#	RAEB-2 (24y, F, XPGaAiVI)	Death at 25y
Berbis et al.,1989 (Bordeaux, France) [24]	2/2	Algeria	XPC: delTG	RAEB-t (27, M, XPGaMVI)	Death at 27y
Tomas et al.,1989 (Spain) [25]	1/1	Spain	NR	Renal leiomyosarcoma (12y, F)	Death at 13y
Salob et al.,1992 (London, UK) [26]	1/1	Pakistan	XP-C	Aplastic anemia as pre-MDS (10y, F)	NR
Visweswara et al.,1997 (Benghazi, Libya) [27]	2/2	Libya	Med Basin	Wilm’s tumor (17y, F)	Death at 18y
Visweswara et al.,1997 (Benghazi, Libya) [27]	2/2	Libya	Med Basin	Wilm’s tumor (16y, F)	Death at 17y
Giglia et al.,1998 and Giglia et al.,1999 (Villejuif, France) [28, 29]	3/19	France and North Africa	XPC: delTG	Anaplastic astrocytoma (7y, M, Tunisia, XP233VI)	Death at 8y
			XPC: delTG	Neuroendocrine thyroid tumor (18y, F, Algeria, XP148VI)	Death at 19y
			XP-V	Gastric adenocarcinoma (48y, F, France, XPGAVI)	Death at 54y
Khatri et al.,1992 and Khatri et al.,1999 (1981–1994, Tripoli, Libya) [30, 31]	2/42	Libya	Med Basin	Follicular carcinoma of thyroid (17y, F)	NR
	2/42	Libya	Med Basin	Lymphatic leukemia (16y, M)	Death at 18y
Leite et al.,2009 (Sao Paulo, Brazil) [32]	1/3	Brazil	XPC: delTG	T-cell lymphoma (3y, M, XP04SP)	Death at 13y
Khan et al.,2006 and Bradford et al.,2011 (1971–2009, Bethesda, United States) [33, 34]	6/106	Different countries	XP-C	Glioblastoma (M, NIH, XP15BE)	Death at 16y
			XPC: c.622-2A > C	Spinal cord astrocytoma (22y, M, Native American, XP23BE)	Death at 31y
			XPC: c.633-2A > G and Arg155X	Glioblastoma (29y, F, Hungarian, XP24BE)	Death at 35y
			XPC: IVS5.1-2A > G	Schwannoma (M, NIH, XP14BE)	Death at 73y
			XPC: c.1132_1133delAA	Uterine adenocarcinoma (F, NIH, XP1BE)	Death at 49y
			XPC: delTG	Infiltrative pontine astrocytoma (9y, M, Tunisia, XP664VI)	Death at 10y
Hadj-Rabia et al.,2013 (Paris and Villejuif, France) [35]	4/31	North Africa	XPC: delTG	T-ALL and AML-6 (12y and 15y, M, Morocco, XP924VI)	Death at 15y
			XPC: delTG	Kidney adenocarcinoma (23y, F, Morocco, XP165VI)	Death at 25y
			XPC: delTG	Cervical sarcoma (18y, F, Morocco, XP269VI)	Death at 23y
			XPC: delTG	Papillary thyroid carcinoma (18y, M, Algeria, XP802VI)	Alive
Janjetovic et al.,2013 (Hamburg, Germany) [36]	1/1	Germany	XP-D	Acute megakaryoblastic leukemia (33y, M)	Death at 34y
Jerbi et al., 2016 (2006–2013, Tunis, Tunisia) [9]	5/64	Tunisia	XPC: delTG	Thyroid carcinoma (13y)	Death at 15y
			XPC: delTG	Thyroid carcinoma (15y)	Death at 29y
			XPC: delTG	Uterine leiomyosarcoma (19y, F)	Alive
			XPC: delTG	Uterine leiomyosarcoma (28y, F)	Death at 29y
			XPC: delTG	Leukemia (9y, F)	Death at 10y
Pintens et al.,2016 (Brussels, Belgium) [37]	2/2**	Morocco	Med Basin	RAEB and AML (28y, F)	Death at 28y
Pintens et al.,2016 (Brussels, Belgium) [37]	2/2**	Morocco	Med Basin	ALL (22y, F)	Death at 25y
Lahlimi et al.,2016 (Morocco) [38]	1/1	Morocco	Med Basin	Nephroblastoma (5y, M)	NR
Fassihi et al., 2016 (2010–2016, London, UK) [39]	2/89	Numerous countries	XPC: p.Arg220X	Glioblastoma multiforme (38y, Middle East, XP21BR)	Death at 39y
Fassihi et al., 2016 (2010–2016, London, UK) [39]	2/89	Numerous countries	XPC: p.Glu726X	Dysembryonic neuroepithelial tumor (21y, M, Bangladesh, XP28BR)	NR
Coulombe et al.,2016 (Paris, France) [40]	1/1	Zimbabwe	XPC: IVS12-1G > C	Gingival squamous cell carcinoma (8y,F)	Death at 10y
Zhang et al.,2018 (Shanghai, China) [41]	1/2^††	China	XPC: p.R718X and p.K431EfsX21	Malignant fibrohistiocytoma (20y, M)	NR
Sarasin et al., 2019 (1983–2015, Villejuif and Paris, France) [42]	10/161	North Africa and Spain	XPC: delTG	AML-4 (27y, M, Morocco, XP10VI)	Death at 28y
			XPC: delTG	AML-6 (16y, M, Tunisia, XP82VI)	Death at 18y
			XPC: delTG	AML-6 (24y, F, Tunisia, XP235VI)	Death at 29y
			XPC: delTG	B-ALL and MDS (7y, F, Morocco, XP309VI)	Death at 10y
			XPC: delTG	RAEB-2 (24y, F, Spain, XP185VI)	Death at 25y
			XPC: delTG	RAEB-t (25y, M, Algeria, XP167VI)	Death at 26y
			XPC: delTG	AML (23y, M, Tunisia, XPAHVI)	Death at 25y
			XPC: delTG	T-ALL (21y, F, Morocco, XP673VI)	Death at 22y
			XPC: delTG	AML (29y, M, Algeria, XP538VI)	Death at 29y
			XPC: delTG	AML-6 (29y, F, Morocco, XP2006VI)	Alive after HSCT
Oetjen et al., 2019 (Bethesda, United States) [43]	4/4	North Africa and NIH	XPC: delTG	Diffuse large B-cell lymphoma (29y, M, North Africa, XP393BE)	Death at 29y
			XPC: delTG	Mixed phenotype acute leukemia (19y, F, Morocco, XP540BE)	Alive at 21y
			XPC: delTG and c.1103_1104delAA	MDS and AML (36y, M, NIH, XP30BE)	Death at 38y
			XPC: c.622-2A > C	MDS (18y, M, NIH, XP243BE)	Death at 20y
Santiago et al., 2020 (2009–2015, Sao Paulo, Brazil) [44]	2/32	Brazil	XPC: delTG	Serous ovary carcinoma (27y, F, 19P0)	Alive
Santiago et al., 2020 (2009–2015, Sao Paulo, Brazil) [44]	2/32	Brazil	XP-V: c.571 A > C	Gastric adenocarcinoma (50y, M, 2P0)	Death at 54y
Yurchenko et al., 2020 (Villejuif, France) [18]	2/2	Algeria and Comoros	XPC: delTG	Uterine rhabdomyosarcoma^$$,^{\|\| \|\|} (16y, F, Algeria, XP2004VI) and AML (22y)	Death at 23y from AML
Yurchenko et al., 2020 (Villejuif, France) [18]	2/2	Algeria and Comoros	XPC: IVS12-1G > C	Breast cancer (30y, F, Comoros, XPMYVI)	Death at 30y
Nikolaev and Sarasin, This paper (2015–2020, Villejuif, France)	9/176^¶¶	North Africa and France	XPC: delTG	Uterine rhabdomyosarcoma^{\|\| \|\|} (16y, F, Algeria, XP2003VI)	Alive
			XPC: delTG	Thyroid carcinoma (17y, F, Algeria, XPAAVI)	Alive
			XPC: delTG	Cerebellar astrocytoma (14y, M, Morocco, XPAdSaVI)	Death at 19y
			XPC: delTG	Ovarian sarcoma (18y, F, Morocco, XPElHaVI)	Death at 22y
			XPC: delTG	Uterine adenomyosarcoma (15y, F, Morocco, XPElKaVI))	Alive
			XPC: delTG	Mediastinal T lymphoma (8y, M, Algeria, XP208VI)	Death at 17y
			XPC: delTG	AML-3 (14y, M, Morocco, XPMaAbVI)	Alive
			XPC: delTG	NK lymphoma (24y, F, Morocco, XP420VI)	Death at 25y
			XP-V: p.Val221ProfsX2	Prostate cancer (60y, M, France, XP819VI)	Alive
Kraemer et al. Personal Communication, 2020 and [45] (Bethesda, United States)	3/137^##	NIH	XPC	Lung cancer (58y, F)	Alive
			XPC	Papillary thyroid carcinoma (36y, F, XP570BE))	Alive
			XPE	Papillary thyroid carcinoma (57y, F, XP437BE)	Alive
Total of XP patients	88			89 tumors on internal organs

HSCT, hematopoietic stem cell transplant; RAEB, refractory anemia with excess of blasts; MDS, myelodysplasia (previously called RAEB); AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; NR, not reported
*By definition, internal tumors are all tumors except skin tumors (Basal Cell Carcinoma, Squamous Cell Carcinoma, malignant melanoma) and their metastases as well as cutaneous angiosarcoma. We have excluded tongue and lip tumors, which are essentially caused by sun exposure in XP patients
^†The tumor types are given as reported in the original publications
^‡We called “Med Basin” XP patients originated from the south part of the Mediterranean see, characterized by early skin cancer development and an absence of neurological deterioration. These patients probably belong to the XP group C and have all chance to exhibit the North African XPC founder mutation described as “delTG” (see below and [13])
^$This patient was described as De Sanctis-Cacchione syndrome, which is mainly associated with XPA mutations but can be eventually mistaken with XP-D patient
^||NR: not reported. At the time of the publications, XP genes were unknown
^¶These patients were seen at NIH (Bethesda, United States) by the group of K.H. Kraemer. They are probably of American origins but this is not explicitly indicated in the publications
^#delTG refers to the founder mutation found in the vast majority of XP-C patients from North Africa (Morocco, Algeria, Tunisia, Libya): c.1643_1644delTG; p.Val548AlafsX572 [9, 13]
**Sisters
^††Monozygotic twins
^$$This patient developed two different unrelated internal tumors
^{|| ||}Monozygotic twins
^¶¶The total number of patients indicated here (176) corresponds to 161 XP patients described already by us [42] where only hematological malignancies were reported, but where some of these XP patients had also other internal tumors but not reported, plus 15 new XP patients since this last publication
^##The NIH American cohort of 137 XP patients has 14 individuals with internal tumors. Thirteen were already published and the publications are indicated in the table. One new patient with lung cancer was indicated to us by Dr. K.H. Kraemer and his group as a personal communication

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