Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer

Figures & data

Table 1 Clinical Characteristics of the Ovarian Cancer Patients

Patient	Age at Diagnosis	Debulking Surgery	First Recurrence	Status	Histology	FIGO 2014 Stage	Germline BRCA1 Variant
Long-term recurrence-free survivors
1	65	Optimal	No	NED at 8 years	HGS	III
2	51	Optimal	No	NED at 9 years	CCC	III
3	60	Optimal	No	NED at 9 years	CCC	III
4	62	Optimal	No	NED at 9 years	HGS	IV
5	50	Optimal	No	NED at 9 years	HGS	III	c.188T>A
6	30	Optimal	No	NED at 11years	SM	III
7	47	Optimal	No	NED at 11years	HGS	III
8	52	Optimal	No	NED at 11 years	HGS	III
9	73	Optimal	No	NED at 13 years	HGS	III
10	47	Optimal	No	NED at 13 years	EM	III
11	56	Optimal	No	NED at 14 years	HGS	IV	c.188T>A
12	52	Optimal	No	NED at 21 years	M	III
13	60	Optimal	No	NED at 23 years	Poor	IV
With early recurrence
14	64	Optimal	Persistent	DOD at 2 years	HGS	IV
15	64	Inoperable	Persistent	AWD at 7 years	HGS	IV
16	51	Optimal	Persistent	NED at 20 years	HGS	IV
17	73	Suboptimal	1 year	AWD at 5 years	HGS	III
18	45	Optimal	1 year	AWD at 9 years	HGS	III
19	47	Optimal	1 year	NED at 12 years	Poor	III	c.188T>A
20	57	Optimal	2 years	DOD at 13 years	TCC	III
21	54	Optimal	2 years	DOD at 6 years	CCC	III
22	53	Optimal	2 years	DOD at 5 years	Poor	III
23	74	Optimal	2 years	NED at 11 years	HGS	III
24	55	Optimal	4 years	NED at 19 years, treatment continued	HGS	III	c.188T>A

Abbreviations: NED, No evidence of disease; DOD, Dead of disease; AWD, Alive with disease; HGS, High-grade serous carcinoma; CCC, Clear cell carcinoma; SM, Seromucinous carcinoma; EM, Endometrioid carcinoma; M, Mucinous carcinoma; Poor, Poorly-differentiated carcinoma; TCC, Transitional cell carcinoma.

Table 2 Representative Single Nucleotide Variants in Exons

	Altered Allele	Reference Allele	Gene	With Early Recurrence (n=11)	Long-Term Recurrence-Free Survivors (n=13)	General Japanese Population
rs2185379	A	G	PRDM1	9.1% (n=1)	61.5% (n=8)	13.8%
rs28687398	G	A	LRRC2	9.1% (n=1)	61.5% (n=8)	18.1%
rs17712299	C	T	ABCA13	9.1% (n=1)	61.5% (n=8)	23.3%
rs7533274	A	G	L1TD1	9.1% (n=1)	61.5% (n=8)	23.4%

Figure 1 Intraperitoneal disseminated ID8 tumors were decreased in mice with germline heterozygous PRDM1 rs2185379. The upper bar graph shows the sum of the tumor weights, and data are shown as the mean±SD. The bottom images show representative images of the abdominal cavity in wild type and germline heterozygous rs2185379 mice (white border, representative tumors in the wild type mouse). *Indicates statistical significance (P<0.05).

Figure 2 T lymphocyte infiltration to allograft ID8 tumors was increased in mice with germline heterozygous PRDM1 rs2185379. (A) The bar graph shows proportions of mice in which the area of distribution of each type of tumor-infiltrating lymphocytes in high-power fields (x100) exceeded 25%. (B) The images show representative immunohistochemical staining of CD8 in wild type and germline heterozygous rs2185379 (black border, lymphocyte infiltration area, x 100). Three mice in which the tumors were too small to evaluate were excluded from the germline heterozygous rs2185379 group. *Indicates statistical significance (P<0.05).

Abbreviations: WT, wild type; Hetero, germline heterozygous rs2185379.